Compendium of Cancer Genome Aberrations

HAEM5:EBV-positive diffuse large B-cell 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>
Detection of clonal IGH and IGK gene rearrangements supports a neoplastic process and helps differentiate EBV-positive DLBCL from reactive, polyclonal B-cell proliferations.<ref>{{Cite journal|title=BlueBooksOnline|url=https://tumourclassification.iarc.who.int/chaptercontent/63/149}}</ref> However, the major oncogenic driver rearrangements seen in other aggressive B-cell lymphoma such as the ‘double/triple-hit’ rearrangements involving ''MYC, BCL2, or BCL6'' are rare in EBV-positive DLBCL<ref>{{Cite journal|last=Liu|first=Hui|last2=Xu-Monette|first2=Zijun Y|last3=Tang|first3=Guilin|last4=Wang|first4=Wei|last5=Kim|first5=Young|last6=Yuan|first6=Ji|last7=Li|first7=Yu|last8=Chen|first8=Weina|last9=Li|first9=Yanping|date=2022|title=EBV+ high-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements: a multi-institutional study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/his.14585|journal=Histopathology|language=en|volume=80|issue=3|pages=575–588|doi=10.1111/his.14585|issn=1365-2559}}</ref><ref name=":1">{{Cite journal|last=Frontzek|first=Fabian|last2=Staiger|first2=Annette M.|last3=Wullenkord|first3=Ramona|last4=Grau|first4=Michael|last5=Zapukhlyak|first5=Myroslav|last6=Kurz|first6=Katrin S.|last7=Horn|first7=Heike|last8=Erdmann|first8=Tabea|last9=Fend|first9=Falko|date=2023-03|title=Molecular profiling of EBV associated diffuse large B-cell lymphoma|url=https://www.nature.com/articles/s41375-022-01804-w|journal=Leukemia|language=en|volume=37|issue=3|pages=670–679|doi=10.1038/s41375-022-01804-w|issn=1476-5551|pmc=9991915|pmid=36604606}}</ref>. Its pathogenesis is driven more by EBV-related mechanisms and distinct genetic alterations than by these characteristic translocations. ''IRF4'' rearrangements involving known partners such as ''IGH'' and more recently ''RHOH'' have also been described in EBV-positive DLBCL<ref name=":0">{{Cite journal|last=Zhang|first=Yuxiu|last2=Li|first2=Anqi|last3=Li|first3=Yimin|last4=Ouyang|first4=Binshen|last5=Wang|first5=Xuan|last6=Zhang|first6=Lei|last7=Xu|first7=Haimin|last8=Gu|first8=Yijin|last9=Lu|first9=Xinyuan|date=2024-11|title=Clinicopathological and Molecular Characteristics of Rare EBV-associated Diffuse Large B-cell Lymphoma With IRF4 Rearrangement|url=https://journals.lww.com/10.1097/PAS.0000000000002301|journal=American Journal of Surgical Pathology|language=en|volume=48|issue=11|pages=1341–1348|doi=10.1097/PAS.0000000000002301|issn=0147-5185}}</ref>. ''RHOH'', is an RHO GTPase family member and negative regulator of cell growth, has been described as a fusion partner in other lymphoid neoplasms but is more commonly linked to non-coding somatic hypermutation in DLBCL<ref name=":0" /> Clinically, morphologically as well as at the molecular level, EBV+DLBCL-''IRF4''-R resemble and behave like EBV+DLBCL<ref name=":0" />
{| class="wikitable sortable"
{| class="wikitable sortable"
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!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
!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).
|-
|<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).
|-
|<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
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|<span class="blue-text">EXAMPLE:</span>
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|<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
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==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|''SOCS1''<ref name=":1" /><ref name=":2">{{Cite journal|last=Gebauer|first=Niklas|last2=Künstner|first2=Axel|last3=Ketzer|first3=Julius|last4=Witte|first4=Hanno M.|last5=Rausch|first5=Tobias|last6=Benes|first6=Vladimir|last7=Zimmermann|first7=Jürgen|last8=Gebauer|first8=Judith|last9=Merz|first9=Hartmut|date=2021-05-26|title=Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing|url=https://www.nature.com/articles/s41408-021-00493-5|journal=Blood Cancer Journal|language=en|volume=11|issue=5|pages=102|doi=10.1038/s41408-021-00493-5|issn=2044-5385|pmc=8155002|pmid=34039950}}</ref><ref name=":3">{{Cite journal|last=Takahashi|first=Takumi|last2=Sawada|first2=Keisuke|last3=Yamashita|first3=Takahisa|last4=Yamamoto|first4=Wataru|last5=Iijima|first5=Yosuke|last6=Adachi|first6=Akiko|last7=Kashimura|first7=Makoto|last8=Tabayashi|first8=Takayuki|last9=Kizaki|first9=Masahiro|date=2025|title=Genetic Profiling Reveals the Distinctions Among MTX-Associated DLBCL, EBV-Positive Mucocutaneous Ulcer, and EBV + DLBCL|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cas.70111|journal=Cancer Science|language=en|volume=116|issue=8|pages=2306–2316|doi=10.1111/cas.70111|issn=1349-7006|pmc=12317404|pmid=40458922}}</ref>


<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|Loss of function aberration in the SH2 domain<ref name=":1" />
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Tumor Suppressor gene<ref>{{Cite journal|last=Liau|first=Nicholas P. D.|last2=Laktyushin|first2=Artem|last3=Lucet|first3=Isabelle S.|last4=Murphy|first4=James M.|last5=Yao|first5=Shenggen|last6=Whitlock|first6=Eden|last7=Callaghan|first7=Kimberley|last8=Nicola|first8=Nicos A.|last9=Kershaw|first9=Nadia J.|date=2018-04-19|title=The molecular basis of JAK/STAT inhibition by SOCS1|url=https://www.nature.com/articles/s41467-018-04013-1|journal=Nature Communications|language=en|volume=9|issue=1|pages=1558|doi=10.1038/s41467-018-04013-1|issn=2041-1723|pmc=5908791|pmid=29674694}}</ref>
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|Common<ref name=":1" /><ref name=":2" /><ref name=":3" />
|<span class="blue-text">EXAMPLE:</span> T
|P, T
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<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).
|SOCS1 mutations, especially affecting SOCS-BOX domain, improve prognosis with better PFS and OS, likely due to their role in modulating the JAK-STAT pathway.<ref>{{Cite journal|last=Zhang|first=Xin-Yi|last2=Xing|first2=Tong-Yao|last3=Hua|first3=Wei|last4=Li|first4=Yue|last5=Kong|first5=Yi-Lin|last6=Pan|first6=Bi-Hui|last7=Zhang|first7=Xin-Yu|last8=Wu|first8=Jia-Zhu|last9=Shen|first9=Hao-Rui|date=2025-08-31|title=Prognostic Role of SOCS1 Mutations in Diffuse Large B-Cell Lymphoma|url=https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2025.420|journal=Cancer Research and Treatment|language=English|doi=10.4143/crt.2025.420|issn=1598-2998}}</ref>
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
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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 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>
 
# https://tumourclassification.iarc.who.int/chaptercontent/63/149
# Liu H, Xu-Monette ZY, Tang G, Wang W, Kim Y, Yuan J, Li Y, Chen W, Li Y, Fedoriw GY, Zhu F, Fang X, Luedke C, Medeiros LJ, Young KH & Hu S (2022) ''Histopathology'' 80, 575–588. <nowiki>https://doi.org/10.1111/his.14585</nowiki> EBV+ high-grade B cell lymphoma with ''MYC'' and ''BCL2'' and/or ''BCL6'' rearrangements: a multi-institutional study
# Frontzek, F., Staiger, A.M., Wullenkord, R. ''et al.'' Molecular profiling of EBV associated diffuse large B-cell lymphoma. ''Leukemia'' 37, 670–679 (2023). <nowiki>https://doi.org/10.1038/s41375-022-01804-w</nowiki>
# Zhang, Yuxiu MD*; Li, Anqi MD, PhD*; Li, Yimin MD, PhD*; Ouyang, Binshen MD, PhD*; Wang, Xuan MD, PhD*; Zhang, Lei MSc*; Xu, Haimin BSMT*; Gu, Yijin MSc*; Lu, Xinyuan MD, PhD†; Dong, Lei MD, PhD*; Yi, Hongmei MD, PhD*; Wang, Chaofu MD, PhD*. Clinicopathological and Molecular Characteristics of Rare EBV-associated Diffuse Large B-cell Lymphoma With IRF4 Rearrangement. The American Journal of Surgical Pathology 48(11):p 1341-1348, November 2024. | DOI: 10.1097/PAS.0000000000002301
# Gebauer, N., Künstner, A., Ketzer, J. ''et al.'' Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing. ''Blood Cancer J.'' 11, 102 (2021). <nowiki>https://doi.org/10.1038/s41408-021-00493-5</nowiki>
# Takahashi, T., Sawada, K., Yamashita, T., Yamamoto, W., Iijima, Y., Adachi, A., Kashimura, M., Tabayashi, T., Kizaki, M., Kaneko, T., Tamaru, J.-i., Higashi, M. and Momose, S. (2025), Genetic Profiling Reveals the Distinctions Among MTX-Associated DLBCL, EBV-Positive Mucocutaneous Ulcer, and EBV + DLBCL. Cancer Sci, 116: 2306-2316. <nowiki>https://doi.org/10.1111/cas.70111</nowiki>
# Liau, N.P.D., Laktyushin, A., Lucet, I.S. ''et al.'' The molecular basis of JAK/STAT inhibition by SOCS1. ''Nat Commun'' 9, 1558 (2018). <nowiki>https://doi.org/10.1038/s41467-018-04013-1</nowiki>  
# Zhang XY, Xing TY, Hua W, Li Y, Kong YL, Pan BH, Zhang XY, Wu JZ, Shen HR, Yin H, Wang L, Li JY, Gao R, Liang JH, Xu W. Prognostic Role of SOCS1 Mutations in Diffuse Large B-Cell Lymphoma. Cancer Res Treat. ;0.0. doi: 10.4143/crt.2025.420


==Notes==
==Notes==
Retrieved from "https://test.ccga.io/index.php/HAEM5:EBV-positive_diffuse_large_B-cell_lymphoma"