| Literature DB >> 33436578 |
Teng Gao1,2, Ryan Ptashkin3, Kelly L Bolton4, Maria Sirenko1, Christopher Fong1, Barbara Spitzer5, Kamal Menghrajani4, Juan E Arango Ossa1,2,5, Yangyu Zhou1,2,5, Elsa Bernard1,2, Max Levine1,2,5, Juan S Medina Martinez1,2,5, Yanming Zhang6, Sebastià Franch-Expósito3, Minal Patel2, Lior Z Braunstein7, Daniel Kelly8, Mariko Yabe3, Ryma Benayed3, Nicole M Caltabellotta2, John Philip9, Ederlinda Paraiso10,11, Simon Mantha12, David B Solit11,13,14, Luis A Diaz13,15, Michael F Berger3,16, Virginia Klimek12,17, Ross L Levine2,4,11,15, Ahmet Zehir3, Sean M Devlin18, Elli Papaemmanuil19,20,21,22.
Abstract
Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7-22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6-33, P < 0.001). Our results suggest that mCA should be considered in conjunction with gene mutations in the surveillance of patients at risk of hematologic neoplasms.Entities:
Mesh：
Year: 2021 PMID： 33436578 PMCID： PMC7804935 DOI： 10.1038/s41467-020-20565-7
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694