Evolution of chromosome-arm aberrations in breast cancer through genetic network rewiring Journal Article
| Authors: | Kuzmin, E.; Baker, T. M.; Lesluyes, T.; Monlong, J.; Abe, K. T.; Coelho, P. P.; Schwartz, M.; Del Corpo, J.; Zou, D.; Morin, G.; Pacis, A.; Yang, Y.; Martinez, C.; Barber, J.; Kuasne, H.; Li, R.; Bourgey, M.; Fortier, A. M.; Davison, P. G.; Omeroglu, A.; Guiot, M. C.; Morris, Q.; Kleinman, C. L.; Huang, S.; Gingras, A. C.; Ragoussis, J.; Bourque, G.; Van Loo, P.; Park, M. |
| Article Title: | Evolution of chromosome-arm aberrations in breast cancer through genetic network rewiring |
| 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. © 2024 The Authors |
| Keywords: | aneuploidy; cancer evolution; triple-negative breast cancer; basal breast cancer; chromosome 4p; cp: cancer; chromosomal arm copy number aberrations; cp: genomics; gck-iii; pdcd10 |
| Journal Title: | Cell Reports |
| Volume: | 43 |
| Issue: | 4 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2024-04-23 |
| Start Page: | 113988 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2024.113988 |
| PROVIDER: | scopus |
| PUBMED: | 38517886 |
| PMCID: | PMC11063629 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work