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 (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=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>
}}</blockquote>


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{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
|B-symptoms (weight loss, fever, night sweats)<ref name=":1" />
 
EXAMPLE B-symptoms (weight loss, fever, night sweats)


EXAMPLE Fatigue
Peripheral and/or Lymphadenopathy<ref name=":1" />


EXAMPLE Lymphadenopathy (uncommon)
Most patients present with advanced stage disease<ref name=":1" />
|-
|-
|'''Laboratory Findings'''
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
|Not specific
 
EXAMPLE Lymphocytosis (low level)
|}
|}




<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
<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" />
*B symptoms of weight loss, fevers, chills<ref name=":1" />
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!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.}}


{| class="wikitable sortable"
{| class="wikitable sortable"
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!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)
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|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>
</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
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**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
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**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>
</blockquote>
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!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.}}
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>:


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<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
<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>
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<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.}}
{| class="wikitable"
{| class="wikitable"
!Gene
!Gene
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<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.}}


*JAK-STAT<ref name=":2" />
*JAK-STAT<ref name=":2" />
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(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 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 />


'''
<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 CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
<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]]