作者
Tyler Funnell, Ciara H O’Flanagan, Marc J Williams, Andrew McPherson, Steven McKinney, Farhia Kabeer, Hakwoo Lee, Sohrab Salehi, Ignacio Vázquez-García, Hongyu Shi, Emily Leventhal, Tehmina Masud, Peter Eirew, Damian Yap, Allen W Zhang, Jamie LP Lim, Beixi Wang, Jazmine Brimhall, Justina Biele, Jerome Ting, Vinci Au, Michael Van Vliet, Yi Fei Liu, Sean Beatty, Daniel Lai, Jenifer Pham, Diljot Grewal, Douglas Abrams, Eliyahu Havasov, Samantha Leung, Viktoria Bojilova, Richard A Moore, Nicole Rusk, Florian Uhlitz, Nicholas Ceglia, Adam C Weiner, Elena Zaikova, J Maxwell Douglas, Dmitriy Zamarin, Britta Weigelt, Sarah H Kim, Arnaud Da Cruz Paula, Jorge S Reis-Filho, Spencer D Martin, Yangguang Li, Hong Xu, Teresa Ruiz de Algara, So Ra Lee, Viviana Cerda Llanos, David G Huntsman, Jessica N McAlpine, Sohrab P Shah, Samuel Aparicio
发表日期
2022/12/1
期刊
Nature
卷号
612
期号
7938
页码范围
106-115
出版商
Nature Publishing Group UK
简介
How cell-to-cell copy number alterations that underpin genomic instability in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer, remains understudied. Here, by applying scaled single-cell whole-genome sequencing to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct ‘foreground’ mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences. In TNBC and HGSC, clone-specific high-level …
学术搜索中的文章
T Funnell, CH O'Flanagan, MJ Williams, A McPherson… - Nature, 2022