研究人员对12222个全基因组测序（WGS）的肿瘤-正常匹配对进行了突变特征分析，这些患者是通过英国国家卫生服务系统（NHS）招募来的。研究人员将这些结果与两个独立的癌症WGS数据集（来自国际癌症基因组联盟（ICGC）和哈特维格医学基金会（HMF）），共涉及18640个全基因组测序的癌症进行对比。这些分析为目前的突变特征统计增加了40个单替换和18个双替换的特征。
结果表明，对于每个器官来说，癌症都有数量有限的常见特征和长尾的罕见特征，并且研究人员提供了一个实用的解决方案，将这种常见与罕见特征的概念应用于未来的分析。
据了解，WGS可以进行全面的癌症基因组分析，揭示突变特征、DNA损伤的印记以及每个病人的癌症中出现的修复过程。
附：英文原文
Title: Substitution mutational signatures in whole-genome–sequenced cancers in the UK population
Author: Andrea Degasperi, Xueqing Zou, Tauanne Dias Amarante, Andrea Martinez-Martinez, Gene Ching Chiek Koh, Joo M. L. Dias, Laura Heskin, Lucia Chmelova, Giuseppe Rinaldi, Valerie Ya Wen Wang, Arjun S. Nanda, Aaron Bernstein, Sophie E. Momen, Jamie Young, Daniel Perez-Gil, Yasin Memari, Cherif Badja, Scott Shooter, Jan Czarnecki, Matthew A. Brown, Helen R. Davies, Genomics England Research Consortium, Serena Nik-Zainal
Issue&Volume: 2022-04-22
Abstract: Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses, revealing mutational signatures, imprints of DNA damage, and repair processes that have arisen in each patient’s cancer. We performed mutational signature analyses on 12,222 whole-genome–sequenced tumor-normal matched pairs from patients recruited via the UK National Health Service (NHS). We contrasted our results with two independent cancer WGS datasets—from the International Cancer Genome Consortium (ICGC) and the Hartwig Medical Foundation (HMF)—involving 18,640 whole-genome–sequenced cancers in total. Our analyses add 40 single and 18 double substitution signatures to the current mutational signature tally. We show for each organ that cancers have a limited number of common signatures and a long tail of rare signatures, and we provide a practical solution for applying this concept of common versus rare signatures to future analyses.
DOI: abl9283
Source: https://www.science.org/doi/10.1126/science.abl9283