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Noncoding mutations cause super-enhancer retargeting resulting in protein synthesis dysregulation during B cell lymphoma progression.
Leeman-Neill, Rebecca J; Song, Dong; Bizarro, Jonathan; Wacheul, Ludivine; Rothschild, Gerson; Singh, Sameer; Yang, Yang; Sarode, Aditya Y; Gollapalli, Kishore; Wu, Lijing; Zhang, Wanwei; Chen, Yiyun; Lauring, Max C; Whisenant, D Eric; Bhavsar, Shweta; Lim, Junghyun; Swerdlow, Steven H; Bhagat, Govind; Zhao, Qian; Berchowitz, Luke E; Lafontaine, Denis L J; Wang, Jiguang; Basu, Uttiya.
Afiliação
  • Leeman-Neill RJ; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Song D; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Bizarro J; SIAT-HKUST Joint Laboratory of Cell Evolution and Digital Health, Shenzhen-Hong Kong Collaborative Innovation Research Institute, Shenzhen, China.
  • Wacheul L; Division of Life Science, Department of Chemical and Biological Engineering, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
  • Rothschild G; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Singh S; RNA Molecular Biology, Fonds de la Recherche Scientifique (F.R.S./FNRS), Université libre de Bruxelles (ULB), Biopark Campus, Gosselies, Belgium.
  • Yang Y; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Sarode AY; Institut für Medizinische Physik und Biophysik, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Gollapalli K; State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China.
  • Wu L; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Zhang W; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Chen Y; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Lauring MC; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Whisenant DE; Division of Life Science, Department of Chemical and Biological Engineering, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
  • Bhavsar S; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Lim J; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Swerdlow SH; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Bhagat G; Department of Pharmacy, School of Pharmacy and Institute of New Drug Development, Jeonbuk National University, Jeonju, Republic of Korea.
  • Zhao Q; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Berchowitz LE; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Lafontaine DLJ; State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China.
  • Wang J; Department of Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Basu U; RNA Molecular Biology, Fonds de la Recherche Scientifique (F.R.S./FNRS), Université libre de Bruxelles (ULB), Biopark Campus, Gosselies, Belgium.
Nat Genet ; 55(12): 2160-2174, 2023 Dec.
Article em En | MEDLINE | ID: mdl-38049665
ABSTRACT
Whole-genome sequencing of longitudinal tumor pairs representing transformation of follicular lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) identified coding and noncoding genomic alterations acquired during lymphoma progression. Many of these transformation-associated alterations recurrently and focally occur at topologically associating domain resident regulatory DNA elements, including H3K4me3 promoter marks located within H3K27ac super-enhancer clusters in B cell non-Hodgkin lymphoma. One region found to undergo recurrent alteration upon transformation overlaps a super-enhancer affecting the expression of the PAX5/ZCCHC7 gene pair. ZCCHC7 encodes a subunit of the Trf4/5-Air1/2-Mtr4 polyadenylation-like complex and demonstrated copy number gain, chromosomal translocation and enhancer retargeting-mediated transcriptional upregulation upon lymphoma transformation. Consequently, lymphoma cells demonstrate nucleolar dysregulation via altered noncoding 5.8S ribosomal RNA processing. We find that a noncoding mutation acquired during lymphoma progression affects noncoding rRNA processing, thereby rewiring protein synthesis leading to oncogenic changes in the lymphoma proteome.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma de Células B / Linfoma Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma de Células B / Linfoma Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos