Compendium of Cancer Genome Aberrations

HAEM5:ALK-negative anaplastic large cell lymphoma: Difference between revisions

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{{DISPLAYTITLE:ALK-negative anaplastic large cell lymphoma}}
{{DISPLAYTITLE:ALK-negative anaplastic large cell lymphoma}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}


<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Anaplastic Large Cell Lymphoma, ALK-Negative]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Anaplastic Large Cell Lymphoma, ALK-Negative]].
}}</blockquote>
}}</blockquote>


<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>
<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>


==Primary Author(s)*==
==Primary Author(s)*==
Line 16: Line 16:


Cedars-Sinai, Los Angeles, CA
Cedars-Sinai, Los Angeles, CA
==WHO Classification of Disease==


__TOC__
==Cancer Category / Type==
*[[HAEM4:Mature T- and NK-cell Neoplasms]]
==Cancer Sub-Classification / Subtype==
*Anaplastic Large Cell Lymphoma, ALK-Negative<ref name=":0" /><ref>{{Cite journal|last=Al|first=Feldman|last2=A|first2=Dogan|last3=Di|first3=Smith|last4=Me|first4=Law|last5=Sm|first5=Ansell|last6=Sh|first6=Johnson|last7=Jc|first7=Porcher|last8=N|first8=Ozsan|last9=Ed|first9=Wieben|date=2011|title=Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing|url=https://pubmed.ncbi.nlm.nih.gov/21030553/|language=en|doi=10.1182/blood-2010-08-303305|pmc=PMC3035081|pmid=21030553}}</ref>
==Definition / Description of Disease==
*Anaplastic large cell lymphomas (ALCL), [[ALK]]-negative, is a CD30+ T-cell lymphoma that is morphologically and immunophenotypically indistinguishable (but lacks ALK protein expression) from [[HAEM5:ALK-positive anaplastic large cell lymphoma|ALK(+) ALCL]]<ref name=":9">{{Cite journal|last=Ad|first=Attygalle|last2=J|first2=Cabeçadas|last3=P|first3=Gaulard|last4=Es|first4=Jaffe|last5=D|first5=de Jong|last6=Yh|first6=Ko|last7=J|first7=Said|last8=W|first8=Klapper|date=2014|title=Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology|url=https://pubmed.ncbi.nlm.nih.gov/24128129/|language=en|doi=10.1111/his.12251|pmc=PMC6364972|pmid=24128129}}</ref><ref name=":7">{{Cite journal|last=Sh|first=Swerdlow|last2=E|first2=Campo|last3=Sa|first3=Pileri|last4=Nl|first4=Harris|last5=H|first5=Stein|last6=R|first6=Siebert|last7=R|first7=Advani|last8=M|first8=Ghielmini|last9=Ga|first9=Salles|date=2016|title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/26980727/|language=en|doi=10.1182/blood-2016-01-643569|pmc=PMC4874220|pmid=26980727}}</ref>
*Three major molecular subtypes of ALK (-) ALCL<ref name=":9" /><ref name=":7" />:
**DUSP22-rearranged subtype (30%)
**TP63-rearranged subtype (8%)
**Triple-negative subtype (DUSP22 negative, TP63 negative, ALK negative)
**Emerging subtypes:
***ERBB4 expression (~25%): mutually exclusive with other rearrangements (TP63, DUSP22, ROS or TYK translocations)<ref name=":4" />
==Synonyms / Terminology==
*N/A
==Epidemiology / Prevalence==
*More common in adults than children (peak incidence 6th decade of life)<ref name=":1">{{Cite journal|last=G|first=Hapgood|last2=Kj|first2=Savage|date=2015|title=The biology and management of systemic anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/25869285/|language=en|pmid=25869285}}</ref>
*Less than 3% of all Non-Hodgkin's lymphoma<ref name=":1" />
*M:F 1.5:1<ref name=":1" />
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
!Structure
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
!Disease
 
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
EXAMPLE Fatigue
 
EXAMPLE Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Book
|EXAMPLE Cytopenias
|Haematolymphoid Tumours (5th ed.)
 
EXAMPLE Lymphocytosis (low level)
|}
 
 
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
 
*B symptoms of weight loss, fevers, chills<ref name=":1" />
*Peripheral and/or abdominal lymphadenopathy<ref name=":1" />
*Most patients present with advanced stage disease<ref name=":1" />
 
</blockquote>
==Sites of Involvement==
 
*Nodal (predominantly abdominal lymphadenopathy) in a sinusoidal pattern
*Extranodal (skin, soft tissue, gastrointestinal, bone) in about 20% of cases
**If involving the skin or GI tract, cases must be distinguished from primary cutaneous ALCL or CD30+ enteropathy-associated/other intestinal T-cell lymphomas, respectively
 
==Morphologic Features==
 
*Tissue effacement by cohesive sheets of large, pleomorphic neoplastic cells, with or without prominent nucleoli, with varying proportions of hallmark cells
*"Hallmark cells"
**Lymphoma cells characterized by eccentric, horseshoe-shaped or kidney-shaped nuclei, often with eosinophilic cytoplasm accentuated near the nucleus
**Usually large in size, but may also be smaller
**Less common that in classic variant of ALK (+) ALCL
*DUSP22-rearranged subtype tends to lack large pleomorphic cells and show smaller, monomorphic cells with central nuclear pseudoinclusions (doughnut cells)
*Intrasinusoidal growth pattern seen in cases with preserved nodal architecture
 
==Immunophenotype==
Immunohistochemical patterns vary by subtype<ref name=":1" /><ref>{{Cite journal|last=M|first=Herling|last2=Gz|first2=Rassidakis|last3=D|first3=Jones|last4=A|first4=Schmitt-Graeff|last5=Ah|first5=Sarris|last6=Lj|first6=Medeiros|date=2004|title=Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria|url=https://pubmed.ncbi.nlm.nih.gov/15116326/|language=en|pmid=15116326}}</ref><ref name=":0" />
 
 
'''DUSP22-rearranged subtype'''
 
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
|Category
|T-cell and NK-cell lymphoid proliferations and lymphomas
|-
|-
|Positive (universal)||CD30*, CD43 (almost universally)
|Family
|-
|Mature T-cell and NK-cell neoplasms
|Negative (universal)||'''ALK''', '''TP63''', EBER, LMP-1
|-
|-
|Positive (frequent)
|Type
|CD2, CD3, CD4+ cases more common than CD8, CD5, Clusterin
|Anaplastic large cell lymphoma
|-
|-
|Negative (frequent)
|Subtype(s)
|TIAI, granzyme B, perforin, EMA, PAX5
|ALK-negative anaplastic large cell lymphoma
|}
|}
<nowiki>*</nowiki>Strong and diffuse CD30 staining; should be equal intensity in all cells


'''TP63-rearranged subtype'''
==Related Terminology==


{| class="wikitable sortable"
{| class="wikitable"
|-
|+
!Finding!!Marker
|Acceptable
|Anaplastic large cell lymphoma, ALK-negative
|-
|-
|Positive (universal)||CD30*, CD43 (almost universally), '''P63''', CD4+ cases more common than CD8
|Not Recommended
|-
|N/A
|Negative (universal)||'''ALK''', EBER, LMP-1
|-
|Positive (frequent)
|CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin, clusterin
|-
|Negative (very frequent)
|EMA
|}
|}
'''Triple-negative subtype''' 


==Gene Rearrangements==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|-
|Positive (universal)||CD30*, CD43 (almost universally), CD2, CD3, CD4+ cases more common than CD8, CD5, TIA1, granzyme B, perforin, EMA
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
 
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|-
|Negative (universal)||'''ALK''', '''P63''', EBER, LMP-1
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
 
 
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>
 
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|-
|Positive (common)
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|EMA, clusterin
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|-
|-
|Negative (frequent)||PAX5, CD20, CD79a, CD15
|
|
|
|
|
|
|
|
|}
|}
==Chromosomal Rearrangements (Gene Fusions)==
Put your text here and fill in the table


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 156: Line 117:
!Notes
!Notes
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|*t(6;7)(p25.3;q32.3)||DUSP22/FRA7H<ref name=":10" />||DUSP22/FRA7H fusion protein||30%<ref name=":0" />
EXAMPLE 30% (add reference)
|No
|Yes
|Yes
|No
|
*<nowiki>*</nowiki> These rearrangements are considered mutually exclusive; however, a single case with both ''DUSP22'' and ''TP63'' rearrangement has been described<ref name=":11" />. Can also be seen in a fraction of other PTCL.
*5-year overall survival > 90%
*Therapeutic Implications
**Multi-agent chemotherapy (CHOEP or CHOP-based) as first-line, with or without radiotherapy of involved site
**High dose chemotherapy and autologous stem cell transplantation for remission
**DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission
**Theoretical:
***Ruxolitinib may be used to target JAK-STAT pathway<ref name=":13" /><ref name=":3" /> (not FDA-approved)
***Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway<ref name=":3" /><ref name=":14" />
|-
|*t(3;3)(q22;q26.2), inv(3)(q26q28)
|TP63/TBL1XR1<ref name=":12" />
|TP63/TBL1XR1 fusion protein
|8%<ref name=":0" />
|No
|No
|Yes
|Yes
|EXAMPLE
|No
 
|
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
*<nowiki>*See t(6;7) notes</nowiki>
*5-year overall survival 17%
|-
|t(10;19)(q24;p13)
|NFKB2/TYK2
|NFKB2/TYK2 fusion protein
|rare<ref name=":2" />
|No
|No
|No
|
*5-year overall survival 42% for cases lacking all DUSP22, TP63 and ALK rearrangements<ref name=":0" /><ref name=":15" />
|-
|t(1;19)(p34;p13)
|PABPC4/TYK2
|PABPC4/TYK2 fusion protein
|rare<ref name=":2" />
|No
|No
|No
|
|-
|t(6;10)(q22;q24)
|NFKB2/ROS1
|NFKB2/ROS1 fusion protein
|rare<ref name=":2" />
|No
|No
|No
|
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 173: Line 179:
!Chromosomal Rearrangement<ref>{{Cite journal|last=Pileri|first=Stefano|date=2011-05-01|title=Faculty Opinions recommendation of Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing.|url=http://dx.doi.org/10.3410/f.10182958.10970056}}</ref><ref>{{Cite journal|last=Da|first=Wada|last2=Me|first2=Law|last3=Ed|first3=Hsi|last4=Dj|first4=Dicaudo|last5=L|first5=Ma|last6=Ms|first6=Lim|last7=Ad|first7=Souza|last8=Ni|first8=Comfere|last9=Rh|first9=Weenig|date=2011|title=Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies|url=https://pubmed.ncbi.nlm.nih.gov/21169992/|language=en|doi=10.1038/modpathol.2010.225|pmc=PMC3122134|pmid=21169992}}</ref>!!Genes in Fusion (5’ or 3’ Segments)!!Prevalence
!Chromosomal Rearrangement<ref>{{Cite journal|last=Pileri|first=Stefano|date=2011-05-01|title=Faculty Opinions recommendation of Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing.|url=http://dx.doi.org/10.3410/f.10182958.10970056}}</ref><ref>{{Cite journal|last=Da|first=Wada|last2=Me|first2=Law|last3=Ed|first3=Hsi|last4=Dj|first4=Dicaudo|last5=L|first5=Ma|last6=Ms|first6=Lim|last7=Ad|first7=Souza|last8=Ni|first8=Comfere|last9=Rh|first9=Weenig|date=2011|title=Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies|url=https://pubmed.ncbi.nlm.nih.gov/21169992/|language=en|doi=10.1038/modpathol.2010.225|pmc=PMC3122134|pmid=21169992}}</ref>!!Genes in Fusion (5’ or 3’ Segments)!!Prevalence
|-
|-
|*t(6;7)(p25.3;q32.3)||DUSP22/FRA7H<ref>{{Cite journal|last=Feldman|first=Andrew L.|last2=Dogan|first2=Ahmet|last3=Smith|first3=David I.|last4=Law|first4=Mark E.|last5=Ansell|first5=Stephen M.|last6=Johnson|first6=Sarah H.|last7=Porcher|first7=Julie C.|last8=Ozsan|first8=Nazan|last9=Wieben|first9=Eric D.|date=2011-01-20|title=Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing|url=https://pubmed.ncbi.nlm.nih.gov/21030553|journal=Blood|volume=117|issue=3|pages=915–919|doi=10.1182/blood-2010-08-303305|issn=1528-0020|pmc=3035081|pmid=21030553}}</ref>||30%<ref name=":0">{{Cite journal|last=Er|first=Parrilla Castellar|last2=Es|first2=Jaffe|last3=Jw|first3=Said|last4=Sh|first4=Swerdlow|last5=Rp|first5=Ketterling|last6=Ra|first6=Knudson|last7=Js|first7=Sidhu|last8=Ed|first8=Hsi|last9=S|first9=Karikehalli|date=2014|title=ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes|url=https://pubmed.ncbi.nlm.nih.gov/24894770/|language=en|doi=10.1182/blood-2014-04-571091|pmc=PMC4148769|pmid=24894770}}</ref>
|*t(6;7)(p25.3;q32.3)||DUSP22/FRA7H<ref name=":10">{{Cite journal|last=Feldman|first=Andrew L.|last2=Dogan|first2=Ahmet|last3=Smith|first3=David I.|last4=Law|first4=Mark E.|last5=Ansell|first5=Stephen M.|last6=Johnson|first6=Sarah H.|last7=Porcher|first7=Julie C.|last8=Ozsan|first8=Nazan|last9=Wieben|first9=Eric D.|date=2011-01-20|title=Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing|url=https://pubmed.ncbi.nlm.nih.gov/21030553|journal=Blood|volume=117|issue=3|pages=915–919|doi=10.1182/blood-2010-08-303305|issn=1528-0020|pmc=3035081|pmid=21030553}}</ref>||30%<ref name=":0">{{Cite journal|last=Er|first=Parrilla Castellar|last2=Es|first2=Jaffe|last3=Jw|first3=Said|last4=Sh|first4=Swerdlow|last5=Rp|first5=Ketterling|last6=Ra|first6=Knudson|last7=Js|first7=Sidhu|last8=Ed|first8=Hsi|last9=S|first9=Karikehalli|date=2014|title=ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes|url=https://pubmed.ncbi.nlm.nih.gov/24894770/|language=en|doi=10.1182/blood-2014-04-571091|pmc=PMC4148769|pmid=24894770}}</ref>
|-
|-
|*t(3;3)(q22;q26.2), inv(3)(q26q28)||TP63/TBL1XR1<ref>{{Cite journal|last=Vasmatzis|first=George|last2=Johnson|first2=Sarah H.|last3=Knudson|first3=Ryan A.|last4=Ketterling|first4=Rhett P.|last5=Braggio|first5=Esteban|last6=Fonseca|first6=Rafael|last7=Viswanatha|first7=David S.|last8=Law|first8=Mark E.|last9=Kip|first9=N. Sertac|date=2012-09-13|title=Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/22855598|journal=Blood|volume=120|issue=11|pages=2280–2289|doi=10.1182/blood-2012-03-419937|issn=1528-0020|pmc=5070713|pmid=22855598}}</ref>||8%<ref name=":0" />
|*t(3;3)(q22;q26.2), inv(3)(q26q28)||TP63/TBL1XR1<ref name=":12">{{Cite journal|last=Vasmatzis|first=George|last2=Johnson|first2=Sarah H.|last3=Knudson|first3=Ryan A.|last4=Ketterling|first4=Rhett P.|last5=Braggio|first5=Esteban|last6=Fonseca|first6=Rafael|last7=Viswanatha|first7=David S.|last8=Law|first8=Mark E.|last9=Kip|first9=N. Sertac|date=2012-09-13|title=Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/22855598|journal=Blood|volume=120|issue=11|pages=2280–2289|doi=10.1182/blood-2012-03-419937|issn=1528-0020|pmc=5070713|pmid=22855598}}</ref>||8%<ref name=":0" />
|-
|-
|t(10;19)(q24;p13)
|t(10;19)(q24;p13)
Line 189: Line 195:
|rare<ref name=":2" />
|rare<ref name=":2" />
|}
|}
<nowiki>*</nowiki> These rearrangements are considered mutually exclusive; however, a single case with both ''DUSP22'' and ''TP63'' rearrangement has been described<ref>{{Cite journal|last=K|first=Karube|last2=Al|first2=Feldman|date=2020|title="Double-hit" of DUSP22 and TP63 rearrangements in anaplastic large cell lymphoma, ALK-negative|url=https://pubmed.ncbi.nlm.nih.gov/32106310/|language=en|pmid=32106310}}</ref>. Can also be seen in a fraction of other PTCL.
<nowiki>*</nowiki> These rearrangements are considered mutually exclusive; however, a single case with both ''DUSP22'' and ''TP63'' rearrangement has been described<ref name=":11">{{Cite journal|last=K|first=Karube|last2=Al|first2=Feldman|date=2020|title="Double-hit" of DUSP22 and TP63 rearrangements in anaplastic large cell lymphoma, ALK-negative|url=https://pubmed.ncbi.nlm.nih.gov/32106310/|language=en|pmid=32106310}}</ref>. Can also be seen in a fraction of other PTCL.


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>




<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
* Gene Mutations (SNV/INDEL)}}</blockquote>


*'''Diagnosis'''  
*'''Diagnosis'''  
**In general, ALK(-) ALCL has a worse prognosis when compared to ALK (+) ALCL<ref name=":7" />
**In general, ALK(-) ALCL has a worse prognosis when compared to ALK (+) ALCL<ref name=":7">{{Cite journal|last=Sh|first=Swerdlow|last2=E|first2=Campo|last3=Sa|first3=Pileri|last4=Nl|first4=Harris|last5=H|first5=Stein|last6=R|first6=Siebert|last7=R|first7=Advani|last8=M|first8=Ghielmini|last9=Ga|first9=Salles|date=2016|title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/26980727/|language=en|doi=10.1182/blood-2016-01-643569|pmc=PMC4874220|pmid=26980727}}</ref>
**ALK(-) ALCL has shown superior prognosis when compared to PTCL, NOS. The 5-year failure-free survival rate was 36% vs 20%, and overall survival rate was 49% vs 32%<ref name=":8" />
**ALK(-) ALCL has shown superior prognosis when compared to PTCL, NOS. The 5-year failure-free survival rate was 36% vs 20%, and overall survival rate was 49% vs 32%<ref name=":8" />


Line 207: Line 216:
**When compared to ALK(+) ALCL, ALK(-) ALCL has a generally poorer prognosis, however:
**When compared to ALK(+) ALCL, ALK(-) ALCL has a generally poorer prognosis, however:
***When stratified for age, prognosis between ALK(-) and ALK(+) ALCL appears similar <ref name=":8">{{Cite journal|last=Kj|first=Savage|last2=Nl|first2=Harris|last3=Jm|first3=Vose|last4=F|first4=Ullrich|last5=Es|first5=Jaffe|last6=Jm|first6=Connors|last7=L|first7=Rimsza|last8=Sa|first8=Pileri|last9=M|first9=Chhanabhai|date=2008|title=ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project|url=https://pubmed.ncbi.nlm.nih.gov/18385450/|language=en|pmid=18385450}}</ref><ref>{{Cite journal|last=D|first=Sibon|last2=M|first2=Fournier|last3=J|first3=Brière|last4=L|first4=Lamant|last5=C|first5=Haioun|last6=B|first6=Coiffier|last7=S|first7=Bologna|last8=P|first8=Morel|last9=J|first9=Gabarre|date=2012|title=Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials|url=https://pubmed.ncbi.nlm.nih.gov/23045585/|language=en|pmid=23045585}}</ref>
***When stratified for age, prognosis between ALK(-) and ALK(+) ALCL appears similar <ref name=":8">{{Cite journal|last=Kj|first=Savage|last2=Nl|first2=Harris|last3=Jm|first3=Vose|last4=F|first4=Ullrich|last5=Es|first5=Jaffe|last6=Jm|first6=Connors|last7=L|first7=Rimsza|last8=Sa|first8=Pileri|last9=M|first9=Chhanabhai|date=2008|title=ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project|url=https://pubmed.ncbi.nlm.nih.gov/18385450/|language=en|pmid=18385450}}</ref><ref>{{Cite journal|last=D|first=Sibon|last2=M|first2=Fournier|last3=J|first3=Brière|last4=L|first4=Lamant|last5=C|first5=Haioun|last6=B|first6=Coiffier|last7=S|first7=Bologna|last8=P|first8=Morel|last9=J|first9=Gabarre|date=2012|title=Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials|url=https://pubmed.ncbi.nlm.nih.gov/23045585/|language=en|pmid=23045585}}</ref>
**5-year overall survival > 90% for DUSP22-rearranged ALK(-) ALCL, 17% for TP63-rearranged ALK(-) ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK rearrangements<ref name=":0" /><ref>{{Cite journal|last=Mb|first=Pedersen|last2=Sj|first2=Hamilton-Dutoit|last3=K|first3=Bendix|last4=Rp|first4=Ketterling|last5=Pp|first5=Bedroske|last6=Im|first6=Luoma|last7=Ca|first7=Sattler|last8=Rl|first8=Boddicker|last9=Nn|first9=Bennani|date=2017|title=DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study|url=https://pubmed.ncbi.nlm.nih.gov/28522440/|language=en|doi=10.1182/blood-2016-12-755496|pmc=PMC5533203|pmid=28522440}}</ref>
**5-year overall survival > 90% for DUSP22-rearranged ALK(-) ALCL, 17% for TP63-rearranged ALK(-) ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK rearrangements<ref name=":0" /><ref name=":15">{{Cite journal|last=Mb|first=Pedersen|last2=Sj|first2=Hamilton-Dutoit|last3=K|first3=Bendix|last4=Rp|first4=Ketterling|last5=Pp|first5=Bedroske|last6=Im|first6=Luoma|last7=Ca|first7=Sattler|last8=Rl|first8=Boddicker|last9=Nn|first9=Bennani|date=2017|title=DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study|url=https://pubmed.ncbi.nlm.nih.gov/28522440/|language=en|doi=10.1182/blood-2016-12-755496|pmc=PMC5533203|pmid=28522440}}</ref>
**Patients with 6q21/PRDM1 and/or 17p loss showed an inferior outcome than patients with normal 6q21 and 17p; not clear if mainly due to [[TP53]] deletion due to study size<ref name=":5" />
**Patients with 6q21/PRDM1 and/or 17p loss showed an inferior outcome than patients with normal 6q21 and 17p; not clear if mainly due to [[TP53]] deletion due to study size<ref name=":5" />
***Often concomitant loss and seen in almost a quarter of cases
***Often concomitant loss and seen in almost a quarter of cases
Line 219: Line 228:
**DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission
**DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission
**Theoretical:
**Theoretical:
***Ruxolitinib may be used to target JAK-STAT pathway<ref>{{Cite journal|last=R|first=Roskoski|date=2016|title=Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases|url=https://pubmed.ncbi.nlm.nih.gov/27473820/|language=en|pmid=27473820}}</ref><ref name=":3">{{Cite journal|last=E|first=Mereu|last2=E|first2=Pellegrino|last3=I|first3=Scarfò|last4=G|first4=Inghirami|last5=R|first5=Piva|date=2017|title=The heterogeneous landscape of ALK negative ALCL|url=https://pubmed.ncbi.nlm.nih.gov/28061468/|language=en|doi=10.18632/oncotarget.14503|pmc=PMC5392347|pmid=28061468}}</ref> (not FDA-approved)
***Ruxolitinib may be used to target JAK-STAT pathway<ref name=":13">{{Cite journal|last=R|first=Roskoski|date=2016|title=Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases|url=https://pubmed.ncbi.nlm.nih.gov/27473820/|language=en|pmid=27473820}}</ref><ref name=":3">{{Cite journal|last=E|first=Mereu|last2=E|first2=Pellegrino|last3=I|first3=Scarfò|last4=G|first4=Inghirami|last5=R|first5=Piva|date=2017|title=The heterogeneous landscape of ALK negative ALCL|url=https://pubmed.ncbi.nlm.nih.gov/28061468/|language=en|doi=10.18632/oncotarget.14503|pmc=PMC5392347|pmid=28061468}}</ref> (not FDA-approved)
***Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway<ref name=":3" /><ref>{{Cite journal|last=A|first=Chaidos|last2=V|first2=Caputo|last3=A|first3=Karadimitris|date=2015|title=Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence|url=https://pubmed.ncbi.nlm.nih.gov/26137204/|language=en|doi=10.1177/2040620715576662|pmc=PMC4480520|pmid=26137204}}</ref>
***Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway<ref name=":3" /><ref name=":14">{{Cite journal|last=A|first=Chaidos|last2=V|first2=Caputo|last3=A|first3=Karadimitris|date=2015|title=Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence|url=https://pubmed.ncbi.nlm.nih.gov/26137204/|language=en|doi=10.1177/2040620715576662|pmc=PMC4480520|pmid=26137204}}</ref>


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Individual Region Genomic Gain / Loss / LOH==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
|-
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>
7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>
chr7
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span>
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|-
|
|
|
|
|
|
|
|}
 


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 235: Line 299:
!Notes
!Notes
|-
|-
|EXAMPLE
|1q
 
|Gain
7
|
|EXAMPLE Loss
|
|EXAMPLE
|No
 
|No
chr7:1- 159,335,973 [hg38]
|No
|EXAMPLE
|
 
*Prevalence 30%
chr7
*Numerous genes affected
|Yes
|-
|Yes
|6p
|Gain
|25.3
|
|No
|No
|No
|
*Prevalence 30%
*Gene affected: ''DUSP22''
|-
|8q
|Gain
|24.22
|
|No
|No
|No
|
*Prevalence 16-23%
*Genes affected: NDRG1, ''PHF20L1, SLA, ST3GAL1, TG, WISP1''
|-
|1p
|Loss
|13.3-p12
36.33-36.32
|
|No
|No
|No
|
*Prevalence 19-26%
|-
|6q
|Loss > CN-LOH
|21
|
|No
|No
|No
|
*Prevalence 35%
*Genes affected: ''PRDM1, ATG5''
|-
|10p
|Loss
|11.23-p11.22
|
|No
|No
|No
|
*Prevalence 23%
|-
|13q
|Loss
|32.3-q33.3
|
|No
|No
|No
|No
|EXAMPLE
|
 
*Prevalence 23%
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
*Genes affected: ''CDC16, CUL4A,FOXO1A, BRCA2, LHFP, LCP1''
|-
|-
|EXAMPLE
|16q
 
|Loss
8
|23.2
|EXAMPLE Gain
|
|EXAMPLE
|No
 
|No
chr8:1-145,138,636 [hg38]
|EXAMPLE
 
chr8
|No
|No
|
*Prevalence 29%
*Genes affected: ''MAF, WWOX''
|-
|17p
|Loss
|13.3-p12
|
|No
|No
|Yes?**
|No
|No
|EXAMPLE
|
 
*Prevalence: 42%
Common recurrent secondary finding for t(8;21) (add reference).
*Gene affected: ''TP53''
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
The pattern of genomic copy number changes and loss of heterozygosity have been described<ref name=":5">{{Cite journal|last=M|first=Boi|last2=A|first2=Rinaldi|last3=I|first3=Kwee|last4=P|first4=Bonetti|last5=M|first5=Todaro|last6=F|first6=Tabbò|last7=R|first7=Piva|last8=Pm|first8=Rancoita|last9=A|first9=Matolcsy|date=2013|title=PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24004669/|language=en|pmid=24004669}}</ref><ref>{{Cite journal|last=G|first=Vasmatzis|last2=Sh|first2=Johnson|last3=Ra|first3=Knudson|last4=Rp|first4=Ketterling|last5=E|first5=Braggio|last6=R|first6=Fonseca|last7=Ds|first7=Viswanatha|last8=Me|first8=Law|last9=Ns|first9=Kip|date=2012|title=Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/22855598/|language=en|doi=10.1182/blood-2012-03-419937|pmc=PMC5070713|pmid=22855598}}</ref><ref>{{Cite journal|last=Y|first=Zeng|last2=Al|first2=Feldman|date=2016|title=Genetics of anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26104084/|language=en|doi=10.3109/10428194.2015.1064530|pmc=PMC4732699|pmid=26104084}}</ref>:
The pattern of genomic copy number changes and loss of heterozygosity have been described<ref name=":5">{{Cite journal|last=M|first=Boi|last2=A|first2=Rinaldi|last3=I|first3=Kwee|last4=P|first4=Bonetti|last5=M|first5=Todaro|last6=F|first6=Tabbò|last7=R|first7=Piva|last8=Pm|first8=Rancoita|last9=A|first9=Matolcsy|date=2013|title=PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24004669/|language=en|pmid=24004669}}</ref><ref>{{Cite journal|last=G|first=Vasmatzis|last2=Sh|first2=Johnson|last3=Ra|first3=Knudson|last4=Rp|first4=Ketterling|last5=E|first5=Braggio|last6=R|first6=Fonseca|last7=Ds|first7=Viswanatha|last8=Me|first8=Law|last9=Ns|first9=Kip|date=2012|title=Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/22855598/|language=en|doi=10.1182/blood-2012-03-419937|pmc=PMC5070713|pmid=22855598}}</ref><ref>{{Cite journal|last=Y|first=Zeng|last2=Al|first2=Feldman|date=2016|title=Genetics of anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26104084/|language=en|doi=10.3109/10428194.2015.1064530|pmc=PMC4732699|pmid=26104084}}</ref>:


Line 305: Line 433:
19%
19%
|-
|-
|'''6q'''
|6q
|'''Loss > CN-LOH;'''
|Loss > CN-LOH;
See also below for somatic mutations
See also below for somatic mutations
|'''21'''
|21
|'''PRDM1''', ATG5
|PRDM1, ATG5
|'''35%'''
|35%
|-
|-
|10p
|10p
Line 330: Line 458:
|29%
|29%
|-
|-
|'''17p'''
|17p
|'''Loss'''
|Loss
|'''13.3-p12'''
|13.3-p12
|'''TP53'''
|TP53
|'''42%'''
|42%
|}
|}


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Characteristic Chromosomal Patterns==
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>


==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
Co-deletion of 1p and 18q
Co-deletion of 1p and 18q
|Yes
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|No
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE:
|
 
|
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|-
|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}
|}
 
<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}


*Gene expression profiling and comparative genomic hybridization studies have shown that ALK(+) and ALK(-) ALCL share restricted genomic signatures and/or preferential genomic aberrations<ref>{{Cite journal|last=Thompson|first=Mary Ann|last2=Stumph|first2=Jennifer|last3=Henrickson|first3=Sarah E.|last4=Rosenwald|first4=Andreas|last5=Wang|first5=Qifu|last6=Olson|first6=Sandy|last7=Brandt|first7=Stephen J.|last8=Roberts|first8=Jeremy|last9=Zhang|first9=Xueqiong|date=2005-05|title=Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/15948116|journal=Human Pathology|volume=36|issue=5|pages=494–504|doi=10.1016/j.humpath.2005.03.004|issn=0046-8177|pmid=15948116}}</ref><ref>{{Cite journal|last=Piccaluga|first=Pier Paolo|last2=Agostinelli|first2=Claudio|last3=Califano|first3=Andrea|last4=Rossi|first4=Maura|last5=Basso|first5=Katia|last6=Zupo|first6=Simonetta|last7=Went|first7=Philip|last8=Klein|first8=Ulf|last9=Zinzani|first9=Pier Luigi|date=2007-03|title=Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets|url=https://pubmed.ncbi.nlm.nih.gov/17304354|journal=The Journal of Clinical Investigation|volume=117|issue=3|pages=823–834|doi=10.1172/JCI26833|issn=0021-9738|pmc=1794115|pmid=17304354}}</ref><ref>{{Cite journal|last=Salaverria|first=Itziar|last2=Beà|first2=Silvia|last3=Lopez-Guillermo|first3=Armando|last4=Lespinet|first4=Virginia|last5=Pinyol|first5=Magda|last6=Burkhardt|first6=Birgit|last7=Lamant|first7=Laurence|last8=Zettl|first8=Andreas|last9=Horsman|first9=Doug|date=2008-03|title=Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18275429|journal=British Journal of Haematology|volume=140|issue=5|pages=516–526|doi=10.1111/j.1365-2141.2007.06924.x|issn=1365-2141|pmid=18275429}}</ref>
*Gene expression profiling and comparative genomic hybridization studies have shown that ALK(+) and ALK(-) ALCL share restricted genomic signatures and/or preferential genomic aberrations<ref>{{Cite journal|last=Thompson|first=Mary Ann|last2=Stumph|first2=Jennifer|last3=Henrickson|first3=Sarah E.|last4=Rosenwald|first4=Andreas|last5=Wang|first5=Qifu|last6=Olson|first6=Sandy|last7=Brandt|first7=Stephen J.|last8=Roberts|first8=Jeremy|last9=Zhang|first9=Xueqiong|date=2005-05|title=Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/15948116|journal=Human Pathology|volume=36|issue=5|pages=494–504|doi=10.1016/j.humpath.2005.03.004|issn=0046-8177|pmid=15948116}}</ref><ref>{{Cite journal|last=Piccaluga|first=Pier Paolo|last2=Agostinelli|first2=Claudio|last3=Califano|first3=Andrea|last4=Rossi|first4=Maura|last5=Basso|first5=Katia|last6=Zupo|first6=Simonetta|last7=Went|first7=Philip|last8=Klein|first8=Ulf|last9=Zinzani|first9=Pier Luigi|date=2007-03|title=Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets|url=https://pubmed.ncbi.nlm.nih.gov/17304354|journal=The Journal of Clinical Investigation|volume=117|issue=3|pages=823–834|doi=10.1172/JCI26833|issn=0021-9738|pmc=1794115|pmid=17304354}}</ref><ref>{{Cite journal|last=Salaverria|first=Itziar|last2=Beà|first2=Silvia|last3=Lopez-Guillermo|first3=Armando|last4=Lespinet|first4=Virginia|last5=Pinyol|first5=Magda|last6=Burkhardt|first6=Birgit|last7=Lamant|first7=Laurence|last8=Zettl|first8=Andreas|last9=Horsman|first9=Doug|date=2008-03|title=Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18275429|journal=British Journal of Haematology|volume=140|issue=5|pages=516–526|doi=10.1111/j.1365-2141.2007.06924.x|issn=1365-2141|pmid=18275429}}</ref>
Line 367: Line 511:
*See other sections.
*See other sections.


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Gene Mutations (SNV / INDEL)==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
|-
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
 
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|<span class="blue-text">EXAMPLE:</span> T
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|-
|
|
|
|
|
|
|
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
 


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC /  TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
!Notes
|-
|-
|EXAMPLE: TP53; Variable LOF mutations
|''TP53''
|TSG
|23%<ref name=":6" />
|No
|N/A
|No
|Yes
|No
|<br />
|-
|''STAT3''
|Oncogene
|26%<ref name=":6" />
|No
|N/A
|No
|Yes
|No
|
*Not seen in PTCL-NOS<ref name=":2" /> or ALK+ ALCL<ref name=":2" /><ref name=":6" />


EXAMPLE:
*Ruxolitinib may be used to target JAK-STAT pathway (not FDA-approved)<ref name=":13" />
 
|-
EGFR; Exon 20 mutations
|''JAK1''
 
|Oncogene
EXAMPLE: BRAF; Activating mutations
|26%<ref name=":6" />
|EXAMPLE: TSG
|No
|EXAMPLE: 20% (COSMIC)
|N/A
 
|No
EXAMPLE: 30% (add Reference)
|Yes
|EXAMPLE: IDH1 R123H
|No
|EXAMPLE: EGFR amplification
|
*Not seen in PTCL-NOS<ref name=":2" /> or ALK+ ALCL<ref name=":2" /><ref name=":6" />
|-
|PRDM1/BLIMP1<ref name=":5" />
|TSG
|6%
|No
|N/A
|No
|No
|No
|
|
|-
|[[NOTCH1]]<ref name=":16" />
|Oncogene
|15%
|No
|No
|No
|No
|No
|
|
|-
|KMT2D<ref name=":6" />
|TSG
|20%
|No
|No
|No
|No
|No
|
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.




<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
{| class="wikitable"
{| class="wikitable"
!Gene
!Gene
Line 424: Line 660:
|
|
|-
|-
|[[NOTCH1]]<ref>{{Cite journal|last=Larose|first=Hugo|last2=Prokoph|first2=Nina|last3=Matthews|first3=Jamie D.|last4=Schlederer|first4=Michaela|last5=Högler|first5=Sandra|last6=Alsulami|first6=Ali F.|last7=Ducray|first7=Stephen P.|last8=Nuglozeh|first8=Edem|last9=Fazaludeen|first9=Feroze M. S.|date=2020-04-23|title=Whole Exome Sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target|url=https://haematologica.org/article/view/9725|journal=Haematologica|language=en|doi=10.3324/haematol.2019.238766|issn=1592-8721}}</ref>
|[[NOTCH1]]<ref name=":16">{{Cite journal|last=Larose|first=Hugo|last2=Prokoph|first2=Nina|last3=Matthews|first3=Jamie D.|last4=Schlederer|first4=Michaela|last5=Högler|first5=Sandra|last6=Alsulami|first6=Ali F.|last7=Ducray|first7=Stephen P.|last8=Nuglozeh|first8=Edem|last9=Fazaludeen|first9=Feroze M. S.|date=2020-04-23|title=Whole Exome Sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target|url=https://haematologica.org/article/view/9725|journal=Haematologica|language=en|doi=10.3324/haematol.2019.238766|issn=1592-8721}}</ref>
|Activating
|Activating
|15%
|15%
Line 446: Line 682:
*Uncommon: FAS, STIM2<ref name=":2" />; LRP1B (9%), EPHA5<ref name=":6" />
*Uncommon: FAS, STIM2<ref name=":2" />; LRP1B (9%), EPHA5<ref name=":6" />


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Epigenomic Alterations==
==Epigenomic Alterations==


Line 453: Line 693:
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|''STAT3''<ref name=":2" />
|EXAMPLE: MAPK signaling
|JAK-STAT pathway
|EXAMPLE: Increased cell growth and proliferation
|Increased cell growth and proliferation
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|''NFkB2-ROS1'' fusion<ref name=":2" />
|EXAMPLE: Cell cycle regulation
|JAK-STAT pathway
|EXAMPLE: Unregulated cell division
|Increased cell growth and proliferation
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|''NFkB2-TYK2'' fusion<ref name=":2" />
|EXAMPLE:  Histone modification, chromatin remodeling
|JAK-STAT pathway
|EXAMPLE:  Abnormal gene expression program
|Increased cell growth and proliferation
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>


*JAK-STAT<ref name=":2" />
*JAK-STAT<ref name=":2" />
Line 478: Line 718:
**When ''JAK/STAT3'' mutations absent, ''NFkB2-ROS1'' and ''NFkB2-TYK2'' fusions may constitutively activate STAT pathway
**When ''JAK/STAT3'' mutations absent, ''NFkB2-ROS1'' and ''NFkB2-TYK2'' fusions may constitutively activate STAT pathway


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Line 500: Line 743:


==Additional Information==
==Additional Information==
This disease is <u>defined/characterized</u> as detailed below:
Anaplastic large cell lymphomas (ALCL), [[ALK]]-negative, is a CD30+ T-cell lymphoma that is morphologically and immunophenotypically indistinguishable (but lacks ALK protein expression) from [[HAEM5:ALK-positive anaplastic large cell lymphoma|ALK(+) ALCL]]<ref name=":9">{{Cite journal|last=Ad|first=Attygalle|last2=J|first2=Cabeçadas|last3=P|first3=Gaulard|last4=Es|first4=Jaffe|last5=D|first5=de Jong|last6=Yh|first6=Ko|last7=J|first7=Said|last8=W|first8=Klapper|date=2014|title=Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology|url=https://pubmed.ncbi.nlm.nih.gov/24128129/|language=en|doi=10.1111/his.12251|pmc=PMC6364972|pmid=24128129}}</ref><ref name=":7" />
*Three major molecular subtypes of ALK (-) ALCL<ref name=":9" /><ref name=":7" />:
**DUSP22-rearranged subtype (30%)
**TP63-rearranged subtype (8%)
**Triple-negative subtype (DUSP22 negative, TP63 negative, ALK negative)
**Emerging subtypes:
***ERBB4 expression (~25%): mutually exclusive with other rearrangements (TP63, DUSP22, ROS or TYK translocations)<ref name=":4" />
The <u>epidemiology/prevalence</u> of this disease is detailed below:
*More common in adults than children (peak incidence 6th decade of life)<ref name=":1">{{Cite journal|last=G|first=Hapgood|last2=Kj|first2=Savage|date=2015|title=The biology and management of systemic anaplastic large cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/25869285/|language=en|pmid=25869285}}</ref>
*Less than 3% of all Non-Hodgkin's lymphoma<ref name=":1" />
*M:F 1.5:1<ref name=":1" />
The <u>clinical features</u> of this disease are detailed below:
Signs and symptoms - B-symptoms (weight loss, fever, night sweats)<ref name=":1" />; Peripheral and/or Lymphadenopathy<ref name=":1" />; Most patients present with advanced stage disease<ref name=":1" />
Laboratory findings - Not specific
The <u>sites of involvement</u> of this disease are detailed below:
*Nodal (predominantly abdominal lymphadenopathy) in a sinusoidal pattern
*Extranodal (skin, soft tissue, gastrointestinal, bone) in about 20% of cases
**If involving the skin or GI tract, cases must be distinguished from primary cutaneous ALCL or CD30+ enteropathy-associated/other intestinal T-cell lymphomas, respectively
The <u>morphologic features</u> of this disease are detailed below:
*Tissue effacement by cohesive sheets of large, pleomorphic neoplastic cells, with or without prominent nucleoli, with varying proportions of hallmark cells
*"Hallmark cells"
**Lymphoma cells characterized by eccentric, horseshoe-shaped or kidney-shaped nuclei, often with eosinophilic cytoplasm accentuated near the nucleus
**Usually large in size, but may also be smaller
**Less common that in classic variant of ALK (+) ALCL
*DUSP22-rearranged subtype tends to lack large pleomorphic cells and show smaller, monomorphic cells with central nuclear pseudoinclusions (doughnut cells)
*Intrasinusoidal growth pattern seen in cases with preserved nodal architecture
The <u>immunophenotype</u> of this disease is detailed below:
Immunohistochemical patterns vary by subtype<ref name=":1" /><ref>{{Cite journal|last=M|first=Herling|last2=Gz|first2=Rassidakis|last3=D|first3=Jones|last4=A|first4=Schmitt-Graeff|last5=Ah|first5=Sarris|last6=Lj|first6=Medeiros|date=2004|title=Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria|url=https://pubmed.ncbi.nlm.nih.gov/15116326/|language=en|pmid=15116326}}</ref><ref name=":0" />


*None
'''DUSP22-rearranged subtype'''
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD30*, CD43 (almost universally)
|-
|Negative (universal)||ALK, TP63, EBER, LMP-1
|-
|Positive (frequent)
|CD2, CD3, CD4+ cases more common than CD8, CD5, Clusterin
|-
|Negative (frequent)
|TIAI, granzyme B, perforin, EMA, PAX5
|}
<nowiki>*</nowiki>Strong and diffuse CD30 staining; should be equal intensity in all cells
 
'''TP63-rearranged subtype'''
 
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD30*, CD43 (almost universally), P63, CD4+ cases more common than CD8
|-
|Negative (universal)||ALK, EBER, LMP-1
|-
|Positive (frequent)
|CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin, clusterin
|-
|Negative (very frequent)
|EMA
|}
'''Triple-negative subtype''' 


{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD30*, CD43 (almost universally), CD2, CD3, CD4+ cases more common than CD8, CD5, TIA1, granzyme B, perforin, EMA
|-
|Negative (universal)||ALK, P63, EBER, LMP-1
|-
|Positive (common)
|EMA, clusterin
|-
|Negative (frequent)||PAX5, CD20, CD79a, CD15
|}
==Links==
==Links==


Line 508: Line 840:


==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />


'''
<br />


==Notes==
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
 
Prior Author(s): 
 
       
<nowiki>*</nowiki>''Citation of this Page'': “ALK-negative anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:ALK-negative_anaplastic_large_cell_lymphoma</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “ALK-negative anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:ALK-negative_anaplastic_large_cell_lymphoma</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases A]]
Retrieved from "https://test.ccga.io/index.php/HAEM5:ALK-negative_anaplastic_large_cell_lymphoma"