Evolution of chromosome-arm aberrations in breast cancer through genetic network rewiring
Abstrak
Summary: 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.
Topik & Kata Kunci
Penulis (29)
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
Akses Cepat
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Cek di sumber asli →- Tahun Terbit
- 2024
- Sumber Database
- DOAJ
- DOI
- 10.1016/j.celrep.2024.113988
- Akses
- Open Access ✓