Compendium of Cancer Genome Aberrations

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{{DISPLAYTITLE:Hairy cell leukaemia}}
{{DISPLAYTITLE:Hairy cell leukaemia}}
 
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 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:Hairy Cell Leukemia]].
<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:Hairy Cell Leukemia]].
}}</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)*==
Snehal Patel, MD, PhD, Michael Lack, DO, Shivani Golem, PhD FACMG


*Michael Lack, DO, Shivani Golem, PhD FACMG
==WHO Classification of Disease==
__TOC__


==Cancer Category / Type==
{| class="wikitable"
 
!Structure
*[[HAEM4:Mature B-Cell Neoplasms|Mature B-Cell Neoplasm]]
!Disease
 
|-
==Cancer Sub-Classification / Subtype==
|Book
 
|Haematolymphoid Tumours (5th ed.)
*Hairy Cell Leukemia
|-
|Category
|B-cell lymphoid proliferations and lymphomas
|-
|Family
|Mature B-cell neoplasms
|-
|Type
|Splenic B-cell lymphomas and leukaemias
|-
|Subtype(s)
|Hairy cell leukaemia
|}
==Related Terminology==


==Definition / Description of Disease==
*Hairy cell leukemia (HCL) is a rare indolent neoplasm of B-cell origin seen mostly in adults
*Name derives from the the hair-like projections of the cytoplasm that surround the cells
*Hairy cells most closely resemble mature lymphoid cells
*Marked splenomegaly and marrow infiltration result in left flank discomfort, fatigue, and susceptibility to infections
*Most respond well to monotherapy with a purine analog or interferon alpha
==Synonyms / Terminology==
*Leukemic reticuloendotheliosis
==Epidemiology / Prevalence==
*Incidence (age adjusted) ~ 0.3/100,000
*2% of lymphoid leukemias
*Median age:  58 years, rarely in patients in their 20s
*Males:Females:  4:1
*Whites >> Blacks
*78% to 92% 5yr survival
*
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref>{{Cite journal|last=Lr|first=Teras|last2=Ce|first2=DeSantis|last3=Jr|first3=Cerhan|last4=Lm|first4=Morton|last5=A|first5=Jemal|last6=Cr|first6=Flowers|date=2016|title=2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes|url=https://pubmed.ncbi.nlm.nih.gov/27618563/|language=en|pmid=27618563}}</ref></blockquote>
==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'''
|+
|
|Acceptable
*Asymptomatic (incidental finding on complete blood counts)
|N/A
*B-symptoms (weight loss, fever, night sweats)
*Fatigue
*Splenic enlargement and discomfort
*Recurrent infections
*Lymphadenopathy (rare)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|Pancytopenia (monocytopenia is characteristic)
|N/A
Lymphocytosis (low level)
|}
|}


 
==Gene Rearrangements==
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: 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>
 
 
'''Signs & Symptoms'''
 
*Asymptomatic (incidental finding on complete blood counts)
*B-symptoms (weight loss, fever, night sweats)
*Fatigue
*Splenic enlargement and discomfort
*Recurrent infections
*Lymphadenopathy (uncommon)
 
'''Laboratory findings'''
 
*Cytopenias
*Monocytopenia
*Lymphocytosis (low level)
 
 
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2">{{Cite journal|last=Grever|first=Michael R.|last2=Abdel-Wahab|first2=Omar|last3=Andritsos|first3=Leslie A.|last4=Banerji|first4=Versha|last5=Barrientos|first5=Jacqueline|last6=Blachly|first6=James S.|last7=Call|first7=Timothy G.|last8=Catovsky|first8=Daniel|last9=Dearden|first9=Claire|date=2017|title=Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia|url=https://ashpublications.org/blood/article/129/5/553/36153/Consensus-guidelines-for-the-diagnosis-and|journal=Blood|language=en|volume=129|issue=5|pages=553–560|doi=10.1182/blood-2016-01-689422|issn=0006-4971|pmc=PMC5290982|pmid=27903528}}</ref></blockquote>
</blockquote>
==Sites of Involvement==
 
 
*Spleen (red pulp)
*Bone marrow
*Liver
*Blood (small number)
 
 
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
==Morphologic Features==
 
 
*Small lymphoid cells
*Abundant pale blue-grey lacey cytoplasm
*Ovoid nuclei ± indentation or folding
*Inconspicuous nucleoli
*Circumferential hairy projections (smear preparations)
*"Fried egg" appearance of cells (tissue sections)
*Marrow (reticulin) fibrosis
 
 
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
==Immunophenotype==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
{| 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
|-
|-
|Positive (B-cell lineage markersl)||CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)
|<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||CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK
|<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||CD5, CD10 (10-20% may be positive), CD23, CD27
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|}
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''




<blockquote class="blockedit">{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
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).
{| class="wikitable"
|-
|-
!Finding!!Marker
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<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
|
|
|-
|-
|Positive (B-cell lineage markers)||CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)
|
|-
|
|Positive
|
|CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK
|
|-
|
|Negative||CD5, CD10 (10-20% may be positive), CD23, CD27
|
|
|
|}
|}
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>
</blockquote>
==Chromosomal Rearrangements (Gene Fusions)==


*No consistent gene fusions
*No consistent gene fusions
*Single case report of IGH-BRAF fusion positive, BRAF p.Val600Glu mutation negative HCL<ref name=":3" />
*Single case report of IGH-BRAF fusion positive, BRAF p.Val600Glu mutation negative HCL<ref name=":3" />
*Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL<ref name=":4" />
*Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL<ref name=":4" />
 
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
 
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}


*No consistent gene fusions
*No consistent gene fusions
Line 158: Line 113:
*Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL<ref name=":4">{{Cite journal|last=Rahman|first=Zaid Abdel|last2=Muwalla|first2=Firas|last3=Jiang|first3=Liuyan|last4=Foran|first4=James|date=2020|title=Hairy cell leukemia with CCND1/IGH fusion gene and BRAF V600E mutation|url=https://www.ncbi.nlm.nih.gov/pubmed/32257795|journal=Leukemia Research Reports|volume=13|pages=100197|doi=10.1016/j.lrr.2020.100197|issn=2213-0489|pmc=7096740|pmid=32257795}}</ref>
*Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL<ref name=":4">{{Cite journal|last=Rahman|first=Zaid Abdel|last2=Muwalla|first2=Firas|last3=Jiang|first3=Liuyan|last4=Foran|first4=James|date=2020|title=Hairy cell leukemia with CCND1/IGH fusion gene and BRAF V600E mutation|url=https://www.ncbi.nlm.nih.gov/pubmed/32257795|journal=Leukemia Research Reports|volume=13|pages=100197|doi=10.1016/j.lrr.2020.100197|issn=2213-0489|pmc=7096740|pmid=32257795}}</ref>


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


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* 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>
{| class="wikitable"
{| class="wikitable"
!Alteration
!Alteration
Line 193: Line 151:
<nowiki>*</nowiki>Not all BRAF mutations confer sensitivity to BRAF inhibitors, even if they are activating mutations<ref>{{Cite journal|last=Bracht|first=Jillian Wilhelmina Paulina|last2=Karachaliou|first2=Niki|last3=Bivona|first3=Trever|last4=Lanman|first4=Richard B.|last5=Faull|first5=Iris|last6=Nagy|first6=Rebecca J.|last7=Drozdowskyj|first7=Ana|last8=Berenguer|first8=Jordi|last9=Fernandez-Bruno|first9=Manuel|date=2019|title=BRAF Mutations Classes I, II, and III in NSCLC Patients Included in the SLLIP Trial: The Need for a New Pre-Clinical Treatment Rationale|url=https://www.ncbi.nlm.nih.gov/pubmed/31533235|journal=Cancers|volume=11|issue=9|doi=10.3390/cancers11091381|issn=2072-6694|pmc=6770188|pmid=31533235}}</ref>.
<nowiki>*</nowiki>Not all BRAF mutations confer sensitivity to BRAF inhibitors, even if they are activating mutations<ref>{{Cite journal|last=Bracht|first=Jillian Wilhelmina Paulina|last2=Karachaliou|first2=Niki|last3=Bivona|first3=Trever|last4=Lanman|first4=Richard B.|last5=Faull|first5=Iris|last6=Nagy|first6=Rebecca J.|last7=Drozdowskyj|first7=Ana|last8=Berenguer|first8=Jordi|last9=Fernandez-Bruno|first9=Manuel|date=2019|title=BRAF Mutations Classes I, II, and III in NSCLC Patients Included in the SLLIP Trial: The Need for a New Pre-Clinical Treatment Rationale|url=https://www.ncbi.nlm.nih.gov/pubmed/31533235|journal=Cancers|volume=11|issue=9|doi=10.3390/cancers11091381|issn=2072-6694|pmc=6770188|pmid=31533235}}</ref>.


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Individual Region Genomic Gain / Loss / LOH==
 
==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"
{| class="wikitable"
Line 223: Line 237:
|}  
|}  


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<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>


*Recurrent gains and losses were found to be absent in HCLs from Chinese patients<ref>{{Cite journal|last=Zhang|first=Rui|last2=Wu|first2=Yongli|last3=Wang|first3=Xianfu|last4=Lu|first4=Xianglan|last5=Li|first5=Yan|last6=Li|first6=Shibo|last7=Yan|first7=Xiaojing|date=2020|title=Difference of genomic copy numbers alterations between hairy cell leukemia-variant and classical hairy cell leukemia: a pilot retrospective study in Chinese|url=https://www.ncbi.nlm.nih.gov/pubmed/32132867|journal=International Journal of Medical Sciences|volume=17|issue=3|pages=325–331|doi=10.7150/ijms.39307|issn=1449-1907|pmc=7053350|pmid=32132867}}</ref>
*Recurrent gains and losses were found to be absent in HCLs from Chinese patients<ref>{{Cite journal|last=Zhang|first=Rui|last2=Wu|first2=Yongli|last3=Wang|first3=Xianfu|last4=Lu|first4=Xianglan|last5=Li|first5=Yan|last6=Li|first6=Shibo|last7=Yan|first7=Xiaojing|date=2020|title=Difference of genomic copy numbers alterations between hairy cell leukemia-variant and classical hairy cell leukemia: a pilot retrospective study in Chinese|url=https://www.ncbi.nlm.nih.gov/pubmed/32132867|journal=International Journal of Medical Sciences|volume=17|issue=3|pages=325–331|doi=10.7150/ijms.39307|issn=1449-1907|pmc=7053350|pmid=32132867}}</ref>
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|}
|}


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Characteristic Chromosomal Patterns==
 
==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"
|-
!Chromosomal Pattern
!Molecular Pathogenesis
!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>
Co-deletion of 1p and 18q
|<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).
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> D, P
|
|
|-
|<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
|
|
|-
|
|
|
|
|
|
|}


IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref name=":7" />.
IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref name=":7" />.


<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.}}</blockquote>


*IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref name=":7">{{Cite journal|last=Arons|first=Evgeny|last2=Kreitman|first2=Robert J.|date=2011|title=Molecular variant of hairy cell leukemia with poor prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/21599610|journal=Leukemia & Lymphoma|volume=52 Suppl 2|pages=99–102|doi=10.3109/10428194.2011.565841|issn=1029-2403|pmid=21599610}}</ref>.
*IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref name=":7">{{Cite journal|last=Arons|first=Evgeny|last2=Kreitman|first2=Robert J.|date=2011|title=Molecular variant of hairy cell leukemia with poor prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/21599610|journal=Leukemia & Lymphoma|volume=52 Suppl 2|pages=99–102|doi=10.3109/10428194.2011.565841|issn=1029-2403|pmid=21599610}}</ref>.


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Gene Mutations (SNV / INDEL)==
 
==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"
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!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
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|}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.
 
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*HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations<ref name=":10">{{Cite journal|last=Xi|first=Liqiang|last2=Arons|first2=Evgeny|last3=Navarro|first3=Winnifred|last4=Calvo|first4=Katherine R.|last5=Stetler-Stevenson|first5=Maryalice|last6=Raffeld|first6=Mark|last7=Kreitman|first7=Robert J.|date=2012|title=Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation|url=https://www.ncbi.nlm.nih.gov/pubmed/22210875|journal=Blood|volume=119|issue=14|pages=3330–3332|doi=10.1182/blood-2011-09-379339|issn=1528-0020|pmc=3321859|pmid=22210875}}</ref> and instead harbor MAP2K1 mutations in most cases<ref name=":11">{{Cite journal|last=Waterfall|first=Joshua J.|last2=Arons|first2=Evgeny|last3=Walker|first3=Robert L.|last4=Pineda|first4=Marbin|last5=Roth|first5=Laura|last6=Killian|first6=J. Keith|last7=Abaan|first7=Ogan D.|last8=Davis|first8=Sean R.|last9=Kreitman|first9=Robert J.|date=2014|title=High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias|url=https://www.ncbi.nlm.nih.gov/pubmed/24241536|journal=Nature Genetics|volume=46|issue=1|pages=8–10|doi=10.1038/ng.2828|issn=1546-1718|pmc=3905739|pmid=24241536}}</ref>
*HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations<ref name=":10">{{Cite journal|last=Xi|first=Liqiang|last2=Arons|first2=Evgeny|last3=Navarro|first3=Winnifred|last4=Calvo|first4=Katherine R.|last5=Stetler-Stevenson|first5=Maryalice|last6=Raffeld|first6=Mark|last7=Kreitman|first7=Robert J.|date=2012|title=Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation|url=https://www.ncbi.nlm.nih.gov/pubmed/22210875|journal=Blood|volume=119|issue=14|pages=3330–3332|doi=10.1182/blood-2011-09-379339|issn=1528-0020|pmc=3321859|pmid=22210875}}</ref> and instead harbor MAP2K1 mutations in most cases<ref name=":11">{{Cite journal|last=Waterfall|first=Joshua J.|last2=Arons|first2=Evgeny|last3=Walker|first3=Robert L.|last4=Pineda|first4=Marbin|last5=Roth|first5=Laura|last6=Killian|first6=J. Keith|last7=Abaan|first7=Ogan D.|last8=Davis|first8=Sean R.|last9=Kreitman|first9=Robert J.|date=2014|title=High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias|url=https://www.ncbi.nlm.nih.gov/pubmed/24241536|journal=Nature Genetics|volume=46|issue=1|pages=8–10|doi=10.1038/ng.2828|issn=1546-1718|pmc=3905739|pmid=24241536}}</ref>


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


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==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>
{| class="wikitable sortable"
{| class="wikitable sortable"
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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Molecular feature!!Pathway!!Pathophysiologic outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|BRAF & MAP2K1 activating mutations
|EXAMPLE: MAPK signaling
(IGH-BRAF fusion, 1 report<ref name=":3" />)
|EXAMPLE: Increased cell growth and proliferation
|MAPK signaling
|Increased cell growth and proliferation
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|CDKN1B inactivating mutations
|EXAMPLE: Cell cycle regulation
(IGH-CCND1 fusion, 1 report<ref name=":4" />)
|EXAMPLE: Unregulated cell division
|Cell cycle regulation
|Unregulated cell division
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|KMT2C & ARID1A inactivating mutaitons
|EXAMPLE:  Histone modification, chromatin remodeling
|Histone modification, chromatin remodeling
|EXAMPLE:  Abnormal gene expression program
|Abnormal gene expression program
|}
|}


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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>
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!Molecular feature
!Molecular feature
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<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
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</blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
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==Additional Information==
==Additional Information==
This disease is <u>defined/characterized</u> as detailed below:
*Hairy cell leukemia (HCL) is a rare indolent neoplasm of B-cell origin seen mostly in adults
*Name derives from the the hair-like projections of the cytoplasm that surround the cells
*Hairy cells most closely resemble mature lymphoid cells
*Marked splenomegaly and marrow infiltration result in left flank discomfort, fatigue, and susceptibility to infections
*Most respond well to monotherapy with a purine analog or interferon alpha


*N/A
The <u>epidemiology/prevalence</u><ref name=":1" /><ref>{{Cite journal|last=Lr|first=Teras|last2=Ce|first2=DeSantis|last3=Jr|first3=Cerhan|last4=Lm|first4=Morton|last5=A|first5=Jemal|last6=Cr|first6=Flowers|date=2016|title=2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes|url=https://pubmed.ncbi.nlm.nih.gov/27618563/|language=en|pmid=27618563}}</ref> of this disease is detailed below:
 
*Incidence (age adjusted) ~ 0.3/100,000
*2% of lymphoid leukemias
*Median age:  58 years, rarely in patients in their 20s
*Males:Females:  4:1
*Whites >> Blacks
*78% to 92% 5yr survival
 
The <u>clinical features</u><ref name=":1" /><ref name=":2">{{Cite journal|last=Grever|first=Michael R.|last2=Abdel-Wahab|first2=Omar|last3=Andritsos|first3=Leslie A.|last4=Banerji|first4=Versha|last5=Barrientos|first5=Jacqueline|last6=Blachly|first6=James S.|last7=Call|first7=Timothy G.|last8=Catovsky|first8=Daniel|last9=Dearden|first9=Claire|date=2017|title=Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia|url=https://ashpublications.org/blood/article/129/5/553/36153/Consensus-guidelines-for-the-diagnosis-and|journal=Blood|language=en|volume=129|issue=5|pages=553–560|doi=10.1182/blood-2016-01-689422|issn=0006-4971|pmc=PMC5290982|pmid=27903528}}</ref> of this disease are detailed below:
 
* Signs and symptoms - Asymptomatic (incidental finding on complete blood counts); B-symptoms (weight loss, fever, night sweats); Fatigue; Splenic enlargement and discomfort; Recurrent infections; Lymphadenopathy (rare)
* Laboratory findings - Pancytopenia (monocytopenia is characteristic); Lymphocytosis (low level)
 
The <u>sites of involvement</u><ref name=":1" /><ref name=":2" /> of this disease are detailed below:
 
*Spleen (red pulp); Bone marrow; Liver; Blood (small number)
 
The <u>morphologic features</u><ref name=":1" /><ref name=":2" /> of this disease are detailed below:
 
*Small lymphoid cells; Abundant pale blue-grey lacey cytoplasm; Ovoid nuclei ± indentation or folding; Inconspicuous nucleoli; Circumferential hairy projections (smear preparations); "Fried egg" appearance of cells (tissue sections); Marrow (reticulin) fibrosis
 
The <u>immunophenotype</u><ref name=":1" /><ref name=":2" /> of this disease is detailed below:
 
Positive ((B-cell lineage markers) -
 
Positive - CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)
 
Positive - CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK
 
Negative - CD5, CD10 (10-20% may be positive), CD23, CD27


==Links==
==Links==
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==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 />


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==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'': “Hairy cell leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Hairy_cell_leukaemia</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Hairy cell leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Hairy_cell_leukaemia</nowiki>.
[[Category:HAEM5]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:DISEASE]]
[[Category:Diseases H]]
[[Category:Diseases H]]
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