دورية أكاديمية
Motive and opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements (an LLMPP study).
| العنوان: | Motive and opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements (an LLMPP study). |
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| المؤلفون: | Hilton LK; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Collinge B; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Ben-Neriah S; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Alduaij W; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Shaalan H; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Weng AP; Terry Fox Laboratory, BC Cancer Research Institute, Vancouver, BC, Canada., Cruz M; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Slack GW; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Farinha P; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Miyata-Takata T; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Boyle M; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Meissner B; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Cook JR; Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH., Ondrejka SL; Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH., Ott G; Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany., Rosenwald A; Institute of Pathology, University of Wurzburg, Wurzburg, Germany., Campo E; Hematopathology Section, Hospital Clinic of Barcelona, Institut d'Investigaciones Biomediques August Pi I Sunyer, University of Barcelona, Barcelona, Spain., Amador C; Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL., Greiner TC; Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE., Raess PW; Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, OR., Song JY; Department of Pathology, City of Hope, Duarte, CA., Inghirami G; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY., Jaffe ES; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Weisenburger DD; Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE., Chan WC; Department of Pathology, City of Hope, Duarte, CA., Beiske K; Department of Pathology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Fu K; Department of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY., Delabie J; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Pittaluga S; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Iqbal J; Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE., Wright G; Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD., Sehn LH; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada., Savage KJ; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada., Mungall AJ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Research Institute, Vancouver, BC, Canada., Feldman AL; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN., Staudt LM; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Steidl C; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada., Rimsza LM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ., Morin RD; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.; Canada's Michael Smith Genome Sciences Centre, BC Cancer Research Institute, Vancouver, BC, Canada., Scott DW; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada. |
| المصدر: | Blood [Blood] 2024 Aug 01; Vol. 144 (5), pp. 525-540. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Proto-Oncogene Proteins c-bcl-2*/genetics , Proto-Oncogene Proteins c-myc*/genetics , Gene Rearrangement*, Humans ; Lymphoma, B-Cell/genetics ; Lymphoma, B-Cell/pathology ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology |
| مستخلص: | Abstract: 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 ("double hit"; 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. |
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| معلومات مُعتمدة: | P01 CA229100 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Proto-Oncogene Proteins c-bcl-2) 0 (Proto-Oncogene Proteins c-myc) 0 (BCL2 protein, human) 0 (MYC protein, human) |
| تواريخ الأحداث: | Date Created: 20240503 Date Completed: 20240801 Latest Revision: 20240810 |
| رمز التحديث: | 20240812 |
| مُعرف محوري في PubMed: | PMC11307266 |
| DOI: | 10.1182/blood.2024024251 |
| PMID: | 38701426 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
|---|---|
| DOI: | 10.1182/blood.2024024251 |