Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis
| العنوان: | Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis |
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| المؤلفون: | Simon Mantha, Michael F. Berger, Ryan Ptashkin, Lior Z. Braunstein, Yangyu Zhou, Ederlinda Paraiso, Barbara Spitzer, Kamal Menghrajani, Ross L. Levine, Mariko Yabe, Ryma Benayed, David B. Solit, Daniel Kelly, John Philip, Juan S. Medina Martinez, Sean M. Devlin, Sebastià Franch-Expósito, Luis A. Diaz, Nicole M. Caltabellotta, Elsa Bernard, Max Levine, Teng Gao, Elli Papaemmanuil, Virginia M. Klimek, Minal Patel, Ahmet Zehir, Yanming Zhang, Kelly L. Bolton, Maria Sirenko, Juan E. Arango Ossa, Christopher J. Fong |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Science, Predictive medicine, General Physics and Astronomy, Gene mutation, Biology, Predictive markers, Somatic evolution in cancer, Risk Assessment, General Biochemistry, Genetics and Molecular Biology, Article, Evolutionary genetics, Clonal Evolution, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neoplasms, Genotype, medicine, Cancer genomics, Humans, Cumulative incidence, Risk factor, Selection, Genetic, Aged, Aged, 80 and over, Chromosome Aberrations, Multidisciplinary, Mosaicism, Cancer, Diagnostic markers, General Chemistry, Middle Aged, medicine.disease, Haematopoiesis, Leukemia, 030104 developmental biology, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Mutation, Cancer research, Clonal Hematopoiesis |
| الوصف: | 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 Patients with solid cancers have high rates of clonal haematopoiesis associated with increased risk of secondary leukemias. Here, by using peripheral blood sequencing data from patients with solid non-hematologic cancer, the authors profile the landscape of mosaic chromosomal alterations and gene mutations, defining patients at high risk of leukemia progression. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::32064e47fe72a93319ba11e24a4dc092Test https://doaj.org/article/86f1527efcbe4a8c928f5380279e4756Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....32064e47fe72a93319ba11e24a4dc092 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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