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

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 del...

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Veröffentlicht in:Cell reports (Cambridge) Jg. 43; H. 4; S. 113988
Hauptverfasser: Kuzmin, Elena, Baker, Toby M., Lesluyes, Tom, Monlong, Jean, Abe, Kento T., Coelho, Paula P., Schwartz, Michael, Del Corpo, Joseph, Zou, Dongmei, Morin, Genevieve, Pacis, Alain, Yang, Yang, Martinez, Constanza, Barber, Jarrett, Kuasne, Hellen, Li, Rui, Bourgey, Mathieu, Fortier, Anne-Marie, Davison, Peter G., Omeroglu, Atilla, Guiot, Marie-Christine, Morris, Quaid, Kleinman, Claudia L., Huang, Sidong, Gingras, Anne-Claude, Ragoussis, Jiannis, Bourque, Guillaume, Van Loo, Peter, Park, Morag
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 23.04.2024
Cell Press
Elsevier
Schlagworte:
aneuploidy
Animals
basal breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer
cancer evolution
Cell Line, Tumor
Cell Proliferation - genetics
chromosomal arm copy number aberrations
chromosome 4p
Chromosome Aberrations
Chromosomes, Human, Pair 4 - genetics
CP: Cancer
CP: Genomics
Female
GCK-III
Gene Regulatory Networks
Humans
Life Sciences
Mice
PDCD10
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - pathology
triple-negative breast cancer
triple-negative breast cancer
chromosomal arm copy number aberrations
chromosome 4p
PDCD10
CP: Cancer
aneuploidy
basal breast cancer
CP: Genomics
cancer evolution
GCK-III
ISSN:2211-1247, 2211-1247
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Zusammenfassung: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. [Display omitted] •Chr4p loss evolves early in TNBC•Chr4p loss enhances growth•C4orf19 (PGCKA1) tumor suppressor Kuzmin et al. report that chromosome 4p loss evolves early in triple-negative breast cancer (TNBC) and is associated with enhanced proliferation. C4orf19 (PGCKA1) is a tumor suppressor. Certain regions, including chr4p, suppress proliferation when overexpressed, differentially implicating network rewiring. This study illuminates the early emergence of complex aneuploid karyotypes in TNBC.
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content type line 23
Present address: Department of Biology, Center for Applied Synthetic Biology, Center for Structural and Functional Genomics, Concordia University, Montreal, QC H4B 1R6, Canada
Present address: Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada
Lead contact
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2024.113988