You are here

Nat Genet DOI:10.1038/s41588-022-01140-w

Molecular map of chronic lymphocytic leukemia and its impact on outcome.

Publication TypeJournal Article
Year of Publication2022
AuthorsKnisbacher, BA, Lin, Z, Hahn, CK, Nadeu, F, Duran-Ferrer, M, Stevenson, KE, Tausch, E, Delgado, J, Barbera-Mourelle, A, Taylor-Weiner, A, Bousquets-Muñoz, P, Diaz-Navarro, A, Dunford, A, Anand, S, Kretzmer, H, Gutierrez-Abril, J, López-Tamargo, S, Fernandes, SM, Sun, C, Sivina, M, Rassenti, LZ, Schneider, C, Li, S, Parida, L, Meissner, A, Aguet, F, Burger, JA, Wiestner, A, Kipps, TJ, Brown, JR, Hallek, M, Stewart, C, Neuberg, DS, Martín-Subero, JI, Puente, XS, Stilgenbauer, S, Wu, CJ, Campo, E, Getz, G
JournalNat Genet
Date Published2022 Aug 04
ISSN1546-1718
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.

DOI10.1038/s41588-022-01140-w
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35927489?dopt=Abstract

Alternate JournalNat Genet
PubMed ID35927489
Grant ListCA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
R50CA251956 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA213442 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
CA206978 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
ALTF 14-2018 / / European Molecular Biology Organization (EMBO) /
T32HL116324 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
Intramural Research Program / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
Intramural Research Program / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
BCLLATLAS/810287 / / EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) /
BCLLATLAS/810287 / / EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) /
BCLLATLAS/810287 / / EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) /
BCLLATLAS/810287 / / EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) /
SFB1074 / / Deutsche Forschungsgemeinschaft (German Research Foundation) /
SFB1074 / / Deutsche Forschungsgemeinschaft (German Research Foundation) /
SFB1074 / / Deutsche Forschungsgemeinschaft (German Research Foundation) /
SAF2017-87811-R / / Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness) /
Moon Shot Program in CLL / / UT | University of Texas MD Anderson Cancer Center (MD Anderson) /
CA016672 / / UT | University of Texas MD Anderson Cancer Center (MD Anderson) /