小柯机器人

美国德克萨斯大学MD安德森癌症中心P. Andrew Futreal等研究人员合作发现，癌症基因组中的体细胞突变分布随三维染色质结构而变化。该研究于2020年10月5日在线发表于国际一流学术期刊《自然—遗传学》。

Title: Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure

Author: Kadir C. Akdemir, Victoria T. Le, Justin M. Kim, Sarah Killcoyne, Devin A. King, Ya-Ping Lin, Yanyan Tian, Akira Inoue, Samirkumar B. Amin, Frederick S. Robinson, Manjunath Nimmakayalu, Rafael E. Herrera, Erica J. Lynn, Kin Chan, Sahil Seth, Leszek J. Klimczak, Moritz Gerstung, Dmitry A. Gordenin, John OBrien, Lei Li, Yonathan Lissanu Deribe, Roel G. Verhaak, Peter J. Campbell, Rebecca Fitzgerald, Ashby J. Morrison, Jesse R. Dixon, P. Andrew Futreal

Issue&Volume: 2020-10-05

Abstract: Somatic mutations in driver genes may ultimately lead to the development of cancer. Understanding how somatic mutations accumulate in cancer genomes and the underlying factors that generate somatic mutations is therefore crucial for developing novel therapeutic strategies. To understand the interplay between spatial genome organization and specific mutational processes, we studied 3,000 tumor–normal-pair whole-genome datasets from 42 different human cancer types. Our analyses reveal that the change in somatic mutational load in cancer genomes is co-localized with topologically-associating-domain boundaries. Domain boundaries constitute a better proxy to track mutational load change than replication timing measurements. We show that different mutational processes lead to distinct somatic mutation distributions where certain processes generate mutations in active domains, and others generate mutations in inactive domains. Overall, the interplay between three-dimensional genome organization and active mutational processes has a substantial influence on the large-scale mutation-rate variations observed in human cancers. Somatic mutational loads in cancer genomes change with chromatin domain boundaries. Different mutational processes lead to distinct somatic mutation distributions in active versus inactive domains, including during tumor evolution.

DOI: 10.1038/s41588-020-0708-0

Source: https://www.nature.com/articles/s41588-020-0708-0

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex