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Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma.
Arthur, Sarah E; Jiang, Aixiang; Grande, Bruno M; Alcaide, Miguel; Cojocaru, Razvan; Rushton, Christopher K; Mottok, Anja; Hilton, Laura K; Lat, Prince Kumar; Zhao, Eric Y; Culibrk, Luka; Ennishi, Daisuke; Jessa, Selin; Chong, Lauren; Thomas, Nicole; Pararajalingam, Prasath; Meissner, Barbara; Boyle, Merrill; Davidson, Jordan; Bushell, Kevin R; Lai, Daniel; Farinha, Pedro; Slack, Graham W; Morin, Gregg B; Shah, Sohrab; Sen, Dipankar; Jones, Steven J M; Mungall, Andrew J; Gascoyne, Randy D; Audas, Timothy E; Unrau, Peter; Marra, Marco A; Connors, Joseph M; Steidl, Christian; Scott, David W; Morin, Ryan D.
Afiliación
  • Arthur SE; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Jiang A; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Grande BM; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Alcaide M; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Cojocaru R; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
  • Rushton CK; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Mottok A; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Hilton LK; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Lat PK; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Zhao EY; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Culibrk L; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Ennishi D; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Jessa S; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Chong L; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Thomas N; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Pararajalingam P; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Meissner B; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Boyle M; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Davidson J; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Bushell KR; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Lai D; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Farinha P; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Slack GW; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Morin GB; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Shah S; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Sen D; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Jones SJM; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
  • Mungall AJ; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
  • Gascoyne RD; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Audas TE; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Unrau P; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Marra MA; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
  • Connors JM; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Steidl C; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
  • Scott DW; Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • Morin RD; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
Nat Commun ; 9(1): 4001, 2018 10 01.
Article en En | MEDLINE | ID: mdl-30275490
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3' UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NF-κB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor protein IIB), primarily in the germinal centre B-cell (GCB) subgroup, correlate with poor patient outcomes suggestive of a novel oncogene. These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Regulación Neoplásica de la Expresión Génica / Genoma Humano / Genes Reguladores / Linfoma de Células B Grandes Difuso Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Regulación Neoplásica de la Expresión Génica / Genoma Humano / Genes Reguladores / Linfoma de Células B Grandes Difuso Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido