英国威康桑格研究所Jyoti Nangalia课题组从系统发育学中推断出骨髓增生性肿瘤的发展史。相关论文于2022年1月20日在线发表在《自然》杂志上。
Author: Williams, Nicholas, Lee, Joe, Mitchell, Emily, Moore, Luiza, Baxter, E. Joanna, Hewinson, James, Dawson, Kevin J., Menzies, Andrew, Godfrey, Anna L., Green, Anthony R., Campbell, Peter J., Nangalia, Jyoti
Issue&Volume: 2022-01-20
Abstract: Mutations in cancer-associated genes drive tumour outgrowth, but our knowledge of the timing of driver mutations and subsequent clonal dynamics is limited1,2,3. Here, using whole-genome sequencing of 1,013 clonal haematopoietic colonies from 12 patients with myeloproliferative neoplasms, we identified 580,133 somatic mutations to reconstruct haematopoietic phylogenies and determine clonal histories. Driver mutations were estimated to occur early in life, including the in utero period. JAK2V617F was estimated to have been acquired by 33 weeks of gestation to 10.8 years of age in 5 patients in whom JAK2V617F was the first event. DNMT3A mutations were acquired by 8 weeks of gestation to 7.6 years of age in 4 patients, and a PPM1D mutation was acquired by 5.8 years of age. Additional genomic events occurred before or following JAK2V617F acquisition and as independent clonal expansions. Sequential driver mutation acquisition was separated by decades across life, often outcompeting ancestral clones. The mean latency between JAK2V617F acquisition and diagnosis was 30 years (range 11–54 years). Estimated historical rates of clonal expansion varied substantially (3% to 190% per year), increased with additional driver mutations, and predicted latency to diagnosis. Our study suggests that early driver mutation acquisition and life-long growth and evolution underlie adult myeloproliferative neoplasms, raising opportunities for earlier intervention and a new model for cancer development.
DOI: 10.1038/s41586-021-04312-6
Source: https://www.nature.com/articles/s41586-021-04312-6
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html