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  Molecular map of chronic lymphocytic leukemia and its impact on outcome

Knisbacher, B. A., Lin, Z., Hahn, C. K., Nadeu, F., Duran-Ferrer, M., Stevenson, K. E., et al. (2022). Molecular map of chronic lymphocytic leukemia and its impact on outcome. Nature Genetics. doi:10.1038/s41588-022-01140-w.

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NatureGenet_Knisbacher et al_2022.pdf (Publisher version), 20MB
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© The Author(s), under exclusive licence to Springer Nature America, Inc. 2022
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 Creators:
Knisbacher, Binyamin A., Author
Lin, Ziao, Author
Hahn, Cynthia K., Author
Nadeu, Ferran , Author
Duran-Ferrer, Martí , Author
Stevenson, Kristen E. , Author
Tausch, Eugen , Author
Delgado, Julio , Author
Barbera-Mourelle, Alex , Author
Taylor-Weiner, Amaro , Author
Bousquets-Muñoz, Pablo, Author
Diaz-Navarro, Ander , Author
Dunford, Andrew , Author
Anand, Shankara , Author
Kretzmer, Helene1, Author           
Gutierrez-Abril, Jesus , Author
López-Tamargo, Sara, Author
Fernandes, Stacey M. , Author
Sun, Clare, Author
Sivina, Mariela , Author
Rassenti, Laura Z. , AuthorSchneider, Christof , AuthorLi, Shuqiang , AuthorParida, Laxmi , AuthorMeissner, Alexander1, Author           Aguet , François , AuthorBurger, Jan A. , AuthorWiestner, Adrian , AuthorKipps, Thomas J. , AuthorBrown, Jennifer R. , AuthorHallek, Michael , AuthorStewart, Chip , AuthorNeuberg, Donna S. , AuthorMartín-Subero , José I., AuthorPuente, Xose S. , AuthorStilgenbauer, Stephan , AuthorWu, Catherine J., AuthorCampo, Elias , AuthorGetz, Gad, Author more..
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1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              

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 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.

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Language(s): eng - English
 Dates: 2022-06-212022-08-04
 Publication Status: Published online
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 Identifiers: DOI: 10.1038/s41588-022-01140-w
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Title: Nature Genetics
  Other : Nature Genet.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America, Inc.
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1061-4036
CoNE: https://pure.mpg.de/cone/journals/resource/954925598609