{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:08:55Z","timestamp":1790784535732,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>When the WHO defined high-grade B-cell lymphoma with MYC and BCL2 and\/or BCL6 rearrangements (HGBL-DH\/TH) as a clinical category, rearrangements were the only structural variant (SV) incorporated. An \"atypical double-hit\" entity has been proposed, encompassing tumors with concurrent MYC and BCL2 SVs other than co-occurring translocations - i.e. copy number variations (CNVs). While the identification of a gene expression signature (DHITsig) shared among tumors harboring MYC and BCL2 rearrangements (HGBL-DH\/TH-BCL2) has confirmed a shared underlying biology, the biological implication of MYC and BCL2 CNVs requires further elucidation. We performed a comprehensive analysis of MYC and BCL2 SVs, as determined by fluorescent in situ hybridization (FISH), in a cohort of 802 de novo tumors with diffuse large B-cell lymphoma (DLBCL) morphology. While BCL2 CNVs were associated with increased expression, MYC CNVs were not. Furthermore, MYC and BCL2 CNVs, in the context of atypical double-hit, did not confer a similar gene expression profile as HGBL-DH\/TH-BCL2. Finally, while MYC IHC has been proposed as a screening tool for FISH testing, two mechanisms were observed that uncoupled MYC rearrangement from IHC positivity. 1) low MYC mRNA expression and 2) false-negative immunohistochemistry (IHC) staining mediated by a single nucleotide polymorphism resulting in an asparagine to serine substitution at the 11th amino acid residue of MYC (MYC-N11S). Taken together, these results support the current exclusion of MYC and BCL2 CNVs from HGBL-DH\/TH and highlight the ability of a molecular based classification system to identify tumors with shared biology that FISH and IHC fail to fully capture.<\/jats:p>","DOI":"10.1182\/blood.2020007193","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T21:57:37Z","timestamp":1604008657000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":16,"title":["Impact of MYC and BCL2 structural variants in tumors of DLBCL morphology and mechanisms of false-negative MYC IHC"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5860-2798","authenticated-orcid":false,"given":"Brett J","family":"Collinge","sequence":"first","affiliation":[{"name":"BC Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2867-4037","authenticated-orcid":false,"given":"Susana","family":"Ben-Neriah","sequence":"additional","affiliation":[{"name":"BC Cancer Agency, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Chong","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merrill","family":"Boyle","sequence":"additional","affiliation":[{"name":"BC Cancer Research Centre, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aixiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"BCCRC, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Miyata-Takata","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-9391","authenticated-orcid":false,"given":"Pedro","family":"Farinha","sequence":"additional","affiliation":[{"name":"British Columbia Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1295-3258","authenticated-orcid":false,"given":"Jeffrey W","family":"Craig","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham W.","family":"Slack","sequence":"additional","affiliation":[{"name":"British Columbia Cancer Agency, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ennishi","sequence":"additional","affiliation":[{"name":"Okayama University Hospital, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Mottok","sequence":"additional","affiliation":[{"name":"University Hospital Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Meissner","sequence":"additional","affiliation":[{"name":"BC Cancer Agency, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Chavez","sequence":"additional","affiliation":[{"name":"BC Cancer Research Centre, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-1425","authenticated-orcid":false,"given":"Alina S.","family":"Gerrie","sequence":"additional","affiliation":[{"name":"University of British Columbia and BC Cancer, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4625-3009","authenticated-orcid":false,"given":"Diego","family":"Villa","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-6480","authenticated-orcid":false,"given":"Ciara L.","family":"Freeman","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-9863","authenticated-orcid":false,"given":"Kerry J.","family":"Savage","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie H.","family":"Sehn","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2932-7800","authenticated-orcid":false,"given":"Ryan D.","family":"Morin","sequence":"additional","affiliation":[{"name":"BC Genome Sciences Centre, Maple Ridge, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0905-2742","authenticated-orcid":false,"given":"Andrew J","family":"Mungall","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy D.","family":"Gascoyne","sequence":"additional","affiliation":[{"name":"British Columbia Cancer Agency, Kelowna, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-7175","authenticated-orcid":false,"given":"Marco A.","family":"Marra","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-7531","authenticated-orcid":false,"given":"Joseph M","family":"Connors","sequence":"additional","affiliation":[{"name":"BC Cancer Centre for Lymphoid Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Steidl","sequence":"additional","affiliation":[{"name":"British Columbia Cancer, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Scott","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, 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