TY - JOUR
T1 - Molecular map of chronic lymphocytic leukemia and its impact on outcome
AU - Knisbacher, Binyamin A.
AU - Lin, Ziao
AU - Hahn, Cynthia K.
AU - Nadeu, Ferran
AU - Duran-Ferrer, Martí
AU - Stevenson, Kristen E.
AU - Tausch, Eugen
AU - Delgado, Julio
AU - Barbera-Mourelle, Alex
AU - Taylor-Weiner, Amaro
AU - Bousquets-Muñoz, Pablo
AU - Diaz-Navarro, Ander
AU - Dunford, Andrew
AU - Anand, Shankara
AU - Kretzmer, Helene
AU - Gutierrez-Abril, Jesus
AU - López-Tamargo, Sara
AU - Fernandes, Stacey M.
AU - Sun, Clare
AU - Sivina, Mariela
AU - Rassenti, Laura Z.
AU - Schneider, Christof
AU - Li, Shuqiang
AU - Parida, Laxmi
AU - Meissner, Alexander
AU - Aguet, François
AU - Burger, Jan A.
AU - Wiestner, Adrian
AU - Kipps, Thomas J.
AU - Brown, Jennifer R.
AU - Hallek, Michael
AU - Stewart, Chip
AU - Neuberg, Donna S.
AU - Martín-Subero, José I.
AU - Puente, Xose S.
AU - Stilgenbauer, Stephan
AU - Wu, Catherine J.
AU - Campo, Elias
AU - Getz, Gad
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
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U2 - 10.1038/s41588-022-01140-w
DO - 10.1038/s41588-022-01140-w
M3 - Article
C2 - 35927489
AN - SCOPUS:85131648057
SN - 1061-4036
VL - 54
SP - 1664
EP - 1674
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -