Knisbacher, Binyamin A., Lin, Ziao ORCID: 0000-0002-8495-6995, Hahn, Cynthia K., Nadeu, Ferran ORCID: 0000-0003-2910-9440, Duran-Ferrer, Marti ORCID: 0000-0003-1666-5819, Stevenson, Kristen E., Tausch, Eugen, Delgado, Julio ORCID: 0000-0002-5157-4376, Barbera-Mourelle, Alex, Taylor-Weiner, Amaro, Bousquets-Munoz, Pablo, Diaz-Navarro, Ander, Dunford, Andrew, Anand, Shankara, Kretzmer, Helene ORCID: 0000-0002-0723-4980, Gutierrez-Abril, Jesus, Lopez-Tamargo, Sara, Fernandes, Stacey M., Sun, Clare, Sivina, Mariela, Rassenti, Laura Z., Schneider, Christof, Li, Shuqiang, Parida, Laxmi, Meissner, Alexander, Aguet, Francois, Burger, Jan A., Wiestner, Adrian, Kipps, Thomas J., Brown, Jennifer R., Hallek, Michael ORCID: 0000-0002-7425-4455, Stewart, Chip, Neuberg, Donna S., Martin-Subero, Jose, I, Puente, Xose S., Stilgenbauer, Stephan, Wu, Catherine J., Campo, Elias and Getz, Gad (2022). Molecular map of chronic lymphocytic leukemia and its impact on outcome. Nature Genet., 54 (11). S. 1664 - 1695. BERLIN: NATURE PORTFOLIO. ISSN 1546-1718

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Abstract

A genomic, transcriptomic and epigenomic analysis of chronic lymphocytic leukemia identifies genetic drivers and molecular subtypes associated with clinical outcomes. 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Knisbacher, Binyamin A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lin, ZiaoUNSPECIFIEDorcid.org/0000-0002-8495-6995UNSPECIFIED
Hahn, Cynthia K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nadeu, FerranUNSPECIFIEDorcid.org/0000-0003-2910-9440UNSPECIFIED
Duran-Ferrer, MartiUNSPECIFIEDorcid.org/0000-0003-1666-5819UNSPECIFIED
Stevenson, Kristen E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tausch, EugenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delgado, JulioUNSPECIFIEDorcid.org/0000-0002-5157-4376UNSPECIFIED
Barbera-Mourelle, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor-Weiner, AmaroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bousquets-Munoz, PabloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diaz-Navarro, AnderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunford, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anand, ShankaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kretzmer, HeleneUNSPECIFIEDorcid.org/0000-0002-0723-4980UNSPECIFIED
Gutierrez-Abril, JesusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Tamargo, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandes, Stacey M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sun, ClareUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sivina, MarielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rassenti, Laura Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, ChristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, ShuqiangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parida, LaxmiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meissner, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aguet, FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burger, Jan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiestner, AdrianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kipps, Thomas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brown, Jennifer R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDorcid.org/0000-0002-7425-4455UNSPECIFIED
Stewart, ChipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuberg, Donna S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin-Subero, Jose, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puente, Xose S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, Catherine J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campo, EliasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Getz, GadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-696919
DOI: 10.1038/s41588-022-01140-w
Journal or Publication Title: Nature Genet.
Volume: 54
Number: 11
Page Range: S. 1664 - 1695
Date: 2022
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CANCER GENES; RNA-BINDING; MUTATIONS; DISCOVERY; PROTEIN; MECHANISMS; EVOLUTION; REVEALS; SAMPLES; FAMILYMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69691

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