Cell Reports (Apr 2024)
Evolution of chromosome-arm aberrations in breast cancer through genetic network rewiring
- 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
Affiliations
- Elena Kuzmin
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada; Corresponding author
- Toby M. Baker
- The Francis Crick Institute, NW1 1AT London, UK
- Tom Lesluyes
- The Francis Crick Institute, NW1 1AT London, UK
- Jean Monlong
- Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; McGill Genome Centre, Montreal, QC H3A 0G1, Canada
- Kento T. Abe
- Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
- Paula P. Coelho
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
- Michael Schwartz
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
- Joseph Del Corpo
- Department of Biology, Concordia University, Montreal, QC H4B 1R6, Canada
- Dongmei Zou
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada
- Genevieve Morin
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
- Alain Pacis
- McGill Genome Centre, Montreal, QC H3A 0G1, Canada; Canadian Centre for Computational Genomics (C3G), McGill University, Montreal, QC H3A 0G1, Canada
- Yang Yang
- Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada
- Constanza Martinez
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada; Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H4A 3T2, Canada
- Jarrett Barber
- Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Vector Institute, Toronto, ON M5G 1M1, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Computational and Systems Biology, Sloan Kettering Institute, New York City, NY 10065, USA
- Hellen Kuasne
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada
- Rui Li
- Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; McGill Genome Centre, Montreal, QC H3A 0G1, Canada
- Mathieu Bourgey
- McGill Genome Centre, Montreal, QC H3A 0G1, Canada; Canadian Centre for Computational Genomics (C3G), McGill University, Montreal, QC H3A 0G1, Canada
- Anne-Marie Fortier
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada
- Peter G. Davison
- Department of Surgery, McGill University, Montreal, QC H3G 1A4, Canada; McGill University Health Centre, Montreal, QC H4A 3J1, Canada
- Atilla Omeroglu
- Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada
- Marie-Christine Guiot
- Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada
- Quaid Morris
- Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Vector Institute, Toronto, ON M5G 1M1, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Computational and Systems Biology, Sloan Kettering Institute, New York City, NY 10065, USA; Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Claudia L. Kleinman
- Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada
- Sidong Huang
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada
- Anne-Claude Gingras
- Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
- Jiannis Ragoussis
- Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; McGill Genome Centre, Montreal, QC H3A 0G1, Canada
- Guillaume Bourque
- Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; McGill Genome Centre, Montreal, QC H3A 0G1, Canada; Canadian Centre for Computational Genomics (C3G), McGill University, Montreal, QC H3A 0G1, Canada
- Peter Van Loo
- The Francis Crick Institute, NW1 1AT London, UK; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Morag Park
- Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H4A 3T2, Canada; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 4
p. 113988
Abstract
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.
