Compendium of Cancer Genome Aberrations

HAEM5:Adult T-cell leukaemia/lymphoma: Difference between revisions

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==Gene Rearrangements==
==Gene Rearrangements==
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>
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|''REL (c-Rel)''
|''REL (c-Rel)''
|3′ truncations (no partner gene; gain-of-function)
|3′ truncations (no partner gene; gain-of-function)<ref>{{Cite journal|last=Kogure|first=Yasunori|last2=Kameda|first2=Takuro|last3=Koya|first3=Junji|last4=Yoshimitsu|first4=Makoto|last5=Nosaka|first5=Kisato|last6=Yasunaga|first6=Jun-ichirou|last7=Imaizumi|first7=Yoshitaka|last8=Watanabe|first8=Mizuki|last9=Saito|first9=Yuki|date=2022-02-17|title=Whole-genome landscape of adult T-cell leukemia/lymphoma|url=https://ashpublications.org/blood/article/139/7/967/477456/Whole-genome-landscape-of-adult-T-cell-leukemia|journal=Blood|language=en|volume=139|issue=7|pages=967–982|doi=10.1182/blood.2021013568|issn=0006-4971|pmc=8854674|pmid=34695199}}</ref>
|C-terminal truncation removes negative-regulatory regions → transcription upregulation/activation of REL → NF-κB pathway activation
|C-terminal truncation removes negative-regulatory regions → transcription upregulation/activation of REL → NF-κB pathway activation
|'''2p16.1''' 3′-end truncating rearrangements
|'''2p16.1''' 3′-end truncating rearrangements
|Recurrent (~13%)
|Recurrent (~13%)
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|No
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|''BCL11B''
|''HELIOS (IKZF2)::BCL11B''
|Transcription-factor fusion likely deregulates T-cell developmental programs
|'''t(2;14)(q34;q32)'''
|Rare (<5%; single-case report<ref>{{Cite journal|last=Fujimoto|first=Rika|last2=Ozawa|first2=Tatsuhiko|last3=Itoyama|first3=Takahiro|last4=Sadamori|first4=Naoki|last5=Kurosawa|first5=Nobuyuki|last6=Isobe|first6=Masaharu|date=2012|title=HELIOS-BCL11B fusion gene involvement in a t(2;14)(q34;q32) in an adult T-cell leukemia patient|url=https://pubmed.ncbi.nlm.nih.gov/22867996|journal=Cancer Genetics|volume=205|issue=7-8|pages=356–364|doi=10.1016/j.cancergen.2012.04.006|issn=2210-7762|pmid=22867996}}</ref>)
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|No
|No
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<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
Tandem duplications of  2q33.2 segments cause formation of CTLA4-CD28 and ICOS-CD28 fusion products that render prolonged co-stimulatory signals<ref name=":1">{{Cite journal|last=Kataoka|first=Keisuke|last2=Nagata|first2=Yasunobu|last3=Kitanaka|first3=Akira|last4=Shiraishi|first4=Yuichi|last5=Shimamura|first5=Teppei|last6=Yasunaga|first6=Jun-Ichirou|last7=Totoki|first7=Yasushi|last8=Chiba|first8=Kenichi|last9=Sato-Otsubo|first9=Aiko|date=2015-11|title=Integrated molecular analysis of adult T cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26437031|journal=Nature Genetics|volume=47|issue=11|pages=1304–1315|doi=10.1038/ng.3415|issn=1546-1718|pmid=26437031}}</ref>.
{| class="wikitable sortable"
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!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
|-
|2q33.2 (Tandem Duplication)
|5’ CTLA/3’CD28
|der(2)
|7%
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|2q33.2 (Tandem Duplication)
|5’ICOS/3’CD28
|der(2)
|7%
|}
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
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</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:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}</blockquote>
ATLL diagnosis can be made based on seropositivity for HTLV-1 and histologically and/or cytologically proven peripheral T cell lymphoma (PTCL). Diagnosis can also be made by quantifying proviral DNA loads (PVLs) in peripheral blood mononuclear cells using real time PCR. PVL of an infected person can range from 0.01 to 50% or higher. Other diagnostic criteria includes appropriate patient demographic information, hypercalcemia, skin lesions and a leukemic phase.
The prognosis of ATLL is largely dependent on the subtype. The acute and lymphomatous subtypes are aggressive, with a median survival of 6.2 months and 10.2 months, respectively. The less-aggressive chronic and smoldering subtypes have a median survival of approximately 4.5 years<ref name=":3">{{Cite journal|last=Shimoyama|first=M.|date=1991-11|title=Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)|url=https://pubmed.ncbi.nlm.nih.gov/1751370|journal=British Journal of Haematology|volume=79|issue=3|pages=428–437|doi=10.1111/j.1365-2141.1991.tb08051.x|issn=0007-1048|pmid=1751370}}</ref>. Prognostic factors include clinical variant, age, serum calcium and LDH levels as well as detection of opportunistic infections of parasitic or viral types and p16 gene deletion and p53 mutation.
As ATLL is resistant to most chemotherapy, there is no standard chemotherapy regimen. High dose combination chemotherapy and bone marrow transplantation have been tried previously<ref>{{Cite journal|last=Hishizawa|first=Masakatsu|last2=Kanda|first2=Junya|last3=Utsunomiya|first3=Atae|last4=Taniguchi|first4=Shuichi|last5=Eto|first5=Tetsuya|last6=Moriuchi|first6=Yukiyoshi|last7=Tanosaki|first7=Ryuji|last8=Kawano|first8=Fumio|last9=Miyazaki|first9=Yasushi|date=2010-08-26|title=Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study|url=https://pubmed.ncbi.nlm.nih.gov/20479287|journal=Blood|volume=116|issue=8|pages=1369–1376|doi=10.1182/blood-2009-10-247510|issn=1528-0020|pmid=20479287}}</ref>. Monoclonal antibody-based therapies against IL-2R (anti-Tac), CCR4 (mogamulizumab) and CD52 (alemtuzumab) have also been attempted along with arsenic trioxide, interferon α and zidovudine<ref>{{Cite journal|last=Hermine|first=Olivier|last2=Ramos|first2=Juan Carlos|last3=Tobinai|first3=Kensei|date=02 2018|title=A Review of New Findings in Adult T-cell Leukemia-Lymphoma: A Focus on Current and Emerging Treatment Strategies|url=https://pubmed.ncbi.nlm.nih.gov/29411267|journal=Advances in Therapy|volume=35|issue=2|pages=135–152|doi=10.1007/s12325-018-0658-4|issn=1865-8652|pmc=5818559|pmid=29411267}}</ref>.
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
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</blockquote>
==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==


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==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==


Cytogenetic studies show that ATLL ofte<ref name=":1" />n has a complex abnormal karyotype without a single distinct abnormality. Observed recurrent abnormalities include trisomy for 3, 7 or 21 and monosomy for X as well as deletion of Y and abnormalities of chromosome 6 and 14. Chromosome 14 rearrangements involving TCRA and TCRD at 14q11 and TCL1 at 14q32 have been documented<ref>{{Cite journal|date=1987-11|title=Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Fifth International Workshop on Chromosomes in Leukemia-Lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/2889485|journal=Blood|volume=70|issue=5|pages=1554–1564|issn=0006-4971|pmid=2889485}}</ref>. Frequent deletions in known fragile sites have been detected in over 500 patients.
Cytogenetic studies show that ATLL ofte<ref name=":1">{{Cite journal|last=Kataoka|first=Keisuke|last2=Nagata|first2=Yasunobu|last3=Kitanaka|first3=Akira|last4=Shiraishi|first4=Yuichi|last5=Shimamura|first5=Teppei|last6=Yasunaga|first6=Jun-Ichirou|last7=Totoki|first7=Yasushi|last8=Chiba|first8=Kenichi|last9=Sato-Otsubo|first9=Aiko|date=2015-11|title=Integrated molecular analysis of adult T cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26437031|journal=Nature Genetics|volume=47|issue=11|pages=1304–1315|doi=10.1038/ng.3415|issn=1546-1718|pmid=26437031}}</ref>n has a complex abnormal karyotype without a single distinct abnormality. Observed recurrent abnormalities include trisomy for 3, 7 or 21 and monosomy for X as well as deletion of Y and abnormalities of chromosome 6 and 14. Chromosome 14 rearrangements involving TCRA and TCRD at 14q11 and TCL1 at 14q32 have been documented<ref>{{Cite journal|date=1987-11|title=Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Fifth International Workshop on Chromosomes in Leukemia-Lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/2889485|journal=Blood|volume=70|issue=5|pages=1554–1564|issn=0006-4971|pmid=2889485}}</ref>. Frequent deletions in known fragile sites have been detected in over 500 patients.
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