| Literature DB >> 35927489 |
Binyamin A Knisbacher1, Ziao Lin1,2, Cynthia K Hahn1,3, Ferran Nadeu4,5, Martí Duran-Ferrer4,5, Kristen E Stevenson6, Eugen Tausch7, Julio Delgado4,5,8, Alex Barbera-Mourelle1,9, Amaro Taylor-Weiner1, Pablo Bousquets-Muñoz10, Ander Diaz-Navarro10, Andrew Dunford1, Shankara Anand1, Helene Kretzmer11, Jesus Gutierrez-Abril12, Sara López-Tamargo10, Stacey M Fernandes3, Clare Sun13, Mariela Sivina14, Laura Z Rassenti15, Christof Schneider7, Shuqiang Li1,3,16, Laxmi Parida17, Alexander Meissner1,11,18, François Aguet1, Jan A Burger14, Adrian Wiestner13, Thomas J Kipps15, Jennifer R Brown3,19, Michael Hallek20,21,22, Chip Stewart1, Donna S Neuberg6, José I Martín-Subero4,5,23,24, Xose S Puente5,10, Stephan Stilgenbauer7, Catherine J Wu25,26,27,28, Elias Campo4,5,24,29, Gad Getz30,31,32,33.
Abstract
Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the 'CLL map,' we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. Discovery of new gene expression subtypes further subcategorized this neoplasm and proved to be independent prognostic factors. Clinical outcomes were associated with a combination of genetic, epigenetic and gene expression features, further advancing our prognostic paradigm. Overall, this work reveals fresh insights into CLL oncogenesis and prognostication.Entities:
Year: 2022 PMID： 35927489 DOI： 10.1038/s41588-022-01140-w
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307