Genomic Complexity Profiling Reveals That HORMAD1 Overexpression Contributes to Homologous Recombination Deficiency in Triple-Negative Breast Cancers

Cancer Discovery
Johnathan A WatkinsAndrew N J Tutt

Abstract

Triple-negative breast cancers (TNBC) are characterized by a wide spectrum of genomic alterations, some of which might be caused by defects in DNA repair processes such as homologous recombination (HR). Despite this understanding, associating particular patterns of genomic instability with response to therapy has been challenging. Here, we show that allelic-imbalanced copy-number aberrations (AiCNA) are more prevalent in TNBCs that respond to platinum-based chemotherapy, thus providing a candidate predictive biomarker for this disease. Furthermore, we show that a high level of AiCNA is linked with elevated expression of a meiosis-associated gene, HORMAD1. Elevated HORMAD1 expression suppresses RAD51-dependent HR and drives the use of alternative forms of DNA repair, the generation of AiCNAs, as well as sensitizing cancer cells to HR-targeting therapies. Our data therefore provide a mechanistic association between HORMAD1 expression, a specific pattern of genomic instability, and an association with response to platinum-based chemotherapy in TNBC. Previous studies have shown correlation between mutational "scars" and sensitivity to platinums extending beyond associations with BRCA1/2 mutation, but do not elucidate the mechanism....Continue Reading

References

Oct 29, 1999·Genes & Development·A J PierceM Jasin
Nov 5, 1999·Molecular Cell·M E MoynahanM Jasin
Dec 22, 1999·British Journal of Cancer·F ForozanS P Ethier
Jan 2, 2003·Molecular and Cellular Biology·Jeremy M Stark, Maria Jasin
Oct 2, 2003·Journal of the National Cancer Institute·William D FoulkesLars A Akslen
Oct 14, 2005·Molecular Biology of the Cell·Hengyao NiuNancy M Hollingsworth
Feb 14, 2006·Cancer Cell·Andrea L RichardsonShridar Ganesan
Apr 6, 2006·Bioinformatics·Ryota Suzuki, Hidetoshi Shimodaira
May 17, 2006·The Journal of Investigative Dermatology·James M Grichnik
Oct 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sven RottenbergJos Jonkers
Dec 23, 2008·International Journal of Cancer. Journal International Du Cancer·Jens K HabermannThomas Ried
Feb 28, 2009·Trends in Molecular Medicine·Musaffe TunaGordon B Mills
Jun 26, 2009·The New England Journal of Medicine·Peter C FongJohann S de Bono
Nov 18, 2009·Molecular Cell·Hengyao NiuNancy M Hollingsworth
Jan 27, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Daniel P SilverJudy E Garber
Sep 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Peter Van LooVessela N Kristensen
Dec 8, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M A VolleberghS C Linn
Apr 12, 2011·Nature Cell Biology·Katrin DanielAttila Tóth
Apr 26, 2012·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hiroshi KogoHiroki Kurahashi
May 1, 2012·Nature Biotechnology·Scott L CarterGad Getz
May 12, 2012·Cancer Discovery·Nicolai J BirkbakAndrea L Richardson
Aug 23, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Zhigang C WangUrsula A Matulonis
Sep 4, 2012·Methods in Molecular Biology·Amanda Gunn, Jeremy M Stark
Sep 25, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Oct 30, 2012·Cancer Discovery·Janneke E JaspersSven Rottenberg
Nov 16, 2012·BMC Genomics·Anita GrigoriadisAndrew Tutt
Feb 9, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Patrycja GazinskaSarah E Pinder
Jul 11, 2013·Journal of Skin Cancer·Scott F LindseyJames M Grichnik
Jul 25, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuqiao ShenAlan Ashworth

❮ Previous
Next ❯

Citations

Jan 22, 2020·Nucleic Acids Research·Koichi SatoAlex N Zelensky
Jan 19, 2016·Nature Reviews. Cancer·Christopher J Lord, Alan Ashworth
Oct 19, 2016·Nature Reviews. Clinical Oncology·Giampaolo BianchiniLuca Gianni
Jul 15, 2017·The Journal of Pathology·Erik OliemullerBeatrice A Howard
Sep 16, 2017·Pathology Oncology Research : POR·Ana C GregórioJoão Nuno Moreira
Aug 28, 2018·Statistical Methods in Medical Research·Pieter SegaertPeter J Rousseeuw
May 19, 2019·Andrology·J Feichtinger, R J McFarlane
Sep 1, 2015·International Journal of Cancer. Journal International Du Cancer·Elodie ManiéMarc-Henri Stern
Nov 8, 2017·Current Treatment Options in Oncology·Alyssa La BelleShaveta Vinayak
Sep 27, 2018·Expert Opinion on Emerging Drugs·Marie RobertMario Campone
Mar 10, 2016·Cancer Metastasis Reviews·Christine DesmedtJanina Kulka
Jun 9, 2016·International Journal of Molecular Sciences·Aaraby Yoheswaran Nielsen, Morten Frier Gjerstorff
May 17, 2017·BMC Genetics·Marta K LabochaWeiwei Zhong
Sep 28, 2018·International Journal of Cancer. Journal International Du Cancer·Catia MioFabio Puglisi
Apr 12, 2017·Expert Opinion on Investigational Drugs·Marie RobertMario Campone
May 27, 2016·Endocrine-related Cancer·Diana Lim, Joanne Ngeow
Feb 20, 2018·Frontiers in Genetics·Venkatesh KancherlaSalvatore Piscuoglio
Jun 19, 2019·Cancer Research·Zhoufeng WangWeimin Li
Oct 25, 2017·Cancer Research·Ramsay J McFarlane, Jane A Wakeman
Nov 12, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chia-Chia LiuXiao-Song Wang
Oct 26, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·O SiposA Grigoriadis
Mar 19, 2021·The Pharmacogenomics Journal·Manar S ShafatJohnathan Watkins
Oct 8, 2018·Trends in Cancer·Zane A Gibbs, Angelique W Whitehurst

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.

Breast Cancer Triple-N

Breast cancer cells have receptors for estrogen, progesterone, HER2 receptors (also called ERBB2). Triple-negative breast cancers do not have any of these receptors. Here are the latest discoveries pertaining to triple-negative breast cancers.