Evolution of chromosome-arm aberrations in breast cancer through genetic network rewiring

通过基因网络重连,乳腺癌中染色体臂畸变的演变

阅读:3
作者:Elena Kuzmin ,Toby M Baker ,Tom Lesluyes ,Jean Monlong ,Kento T Abe ,Paula P Coelho ,Michael Schwartz ,Joseph Del Corpo ,Dongmei Zou ,Genevieve Morin ,Alain Pacis ,Yang Yang ,Constanza Martinez ,Jarrett Barber ,Hellen Kuasne ,Rui Li ,Mathieu Bourgey ,Anne-Marie Fortier ,Peter G Davison ,Atilla Omeroglu ,Marie-Christine Guiot ,Quaid Morris ,Claudia L Kleinman ,Sidong Huang ,Anne-Claude Gingras ,Jiannis Ragoussis ,Guillaume Bourque ,Peter Van Loo ,Morag Park

Abstract

The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation. Gene function studies identify an unknown gene, C4orf19, within chr4p, which suppresses proliferation when overexpressed-a member of the PDCD10-GCKIII kinase module we name PGCKA1. Genome-wide pooled overexpression screens using a barcoded library of human open reading frames identify chromosomal regions, including chr4p, that suppress proliferation when overexpressed in a context-dependent manner, implicating network interactions. Together, these results shed light on the early emergence of complex aneuploid karyotypes involving chr4p and adaptive landscapes shaping breast cancer genomes.

特别声明

1、本页面内容包含部分的内容是基于公开信息的合理引用;引用内容仅为补充信息,不代表本站立场。

2、若认为本页面引用内容涉及侵权,请及时与本站联系,我们将第一时间处理。

3、其他媒体/个人如需使用本页面原创内容,需注明“来源:[生知库]”并获得授权;使用引用内容的,需自行联系原作者获得许可。

4、投稿及合作请联系:info@biocloudy.com。