{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:13:07Z","timestamp":1792815187872,"version":"4.5.0"},"reference-count":73,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements (\u201cdouble hit\u201d; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated. Here, we used custom targeted capture and\/or whole-genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, although BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because 1 IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B-cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024024251","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T20:15:31Z","timestamp":1714767331000},"page":"525-540","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":41,"title":["Motive and opportunity: <i>MYC<\/i> rearrangements in high-grade B-cell lymphoma with <i>MYC<\/i> and <i>BCL2<\/i> rearrangements (an LLMPP study)"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6413-6586","authenticated-orcid":false,"given":"Laura K.","family":"Hilton","sequence":"first","affiliation":[{"name":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"},{"name":"2Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5860-2798","authenticated-orcid":false,"given":"Brett","family":"Collinge","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"},{"name":"3Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Ben-Neriah","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2365-5371","authenticated-orcid":false,"given":"Waleed","family":"Alduaij","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haya","family":"Shaalan","sequence":"additional","affiliation":[{"name":"2Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7394-5425","authenticated-orcid":false,"given":"Andrew P.","family":"Weng","sequence":"additional","affiliation":[{"name":"4Terry Fox Laboratory, BC Cancer Research Institute, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Cruz","sequence":"additional","affiliation":[{"name":"2Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham W.","family":"Slack","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"},{"name":"3Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, 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":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"},{"name":"3Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Miyata-Takata","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-0103","authenticated-orcid":false,"given":"Merrill","family":"Boyle","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Meissner","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-8085","authenticated-orcid":false,"given":"James R.","family":"Cook","sequence":"additional","affiliation":[{"name":"5Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-2889","authenticated-orcid":false,"given":"Sarah L.","family":"Ondrejka","sequence":"additional","affiliation":[{"name":"5Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"German","family":"Ott","sequence":"additional","affiliation":[{"name":"6Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Rosenwald","sequence":"additional","affiliation":[{"name":"7Institute of Pathology, University of Wurzburg, Wurzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9850-9793","authenticated-orcid":false,"given":"Elias","family":"Campo","sequence":"additional","affiliation":[{"name":"8Hematopathology Section, Hospital Clinic of Barcelona, Institut d\u2019Investigaciones Biomediques August Pi I Sunyer, University of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0352-5526","authenticated-orcid":false,"given":"Catalina","family":"Amador","sequence":"additional","affiliation":[{"name":"9Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, 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