Identification of DNA methylation biomarkers with potential to predict response to neoadjuvant chemotherapy in triple-negative breast cancer

Braydon Meyer; Samuel Clifton; Warwick Locke; Phuc-Loi Luu; Qian Du; Dilys Lam; Nicola J Armstrong; Beena Kumar; Niantao Deng; Kate Harvey; Alex Swarbrick; Vinod Ganju; Susan J Clark; Ruth Pidsley; Clare Stirzaker

doi:10.1186/s13148-021-01210-6

Identification of DNA methylation biomarkers with potential to predict response to neoadjuvant chemotherapy in triple-negative breast cancer

Clin Epigenetics. 2021 Dec 18;13(1):226. doi: 10.1186/s13148-021-01210-6.

Authors

Braydon Meyer¹, Samuel Clifton¹, Warwick Locke², Phuc-Loi Luu^{1

3}, Qian Du^{1

3}, Dilys Lam¹, Nicola J Armstrong⁴, Beena Kumar^{5

6

7}, Niantao Deng^{3

8}, Kate Harvey⁸, Alex Swarbrick^{3

8}, Vinod Ganju^#⁵, Susan J Clark^#^{9

10}, Ruth Pidsley^#^{11

12}, Clare Stirzaker^#^{13

14}

Affiliations

¹ Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia.
² Molecular Diagnostics Solutions, CSIRO Health and Biosecurity, New South Wales, North Ryde, 2113, Australia.
³ St. Vincent's Clinical School, UNSW Australia, Sydney, NSW, 2010, Australia.
⁴ Department of Mathematics and Statistics, Curtin University, Perth, WA, 6103, Australia.
⁵ Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
⁶ Monash Health Pathology, Monash Health, Victoria, 3168, Australia.
⁷ Monash University, Melbourne, VIC, 3168, Australia.
⁸ Cancer Research Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
⁹ Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia. s.clark@garvan.org.au.
¹⁰ St. Vincent's Clinical School, UNSW Australia, Sydney, NSW, 2010, Australia. s.clark@garvan.org.au.
¹¹ Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia. r.pidsley@garvan.org.au.
¹² St. Vincent's Clinical School, UNSW Australia, Sydney, NSW, 2010, Australia. r.pidsley@garvan.org.au.
¹³ Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia. c.stirzaker@garvan.org.au.
¹⁴ St. Vincent's Clinical School, UNSW Australia, Sydney, NSW, 2010, Australia. c.stirzaker@garvan.org.au.

^# Contributed equally.

Abstract

Neoadjuvant chemotherapy (NAC) is used to treat triple-negative breast cancer (TNBC) prior to resection. Biomarkers that accurately predict a patient's response to NAC are needed to individualise therapy and avoid chemotoxicity from unnecessary chemotherapy. We performed whole-genome DNA methylation profiling on diagnostic TNBC biopsy samples from the Sequential Evaluation of Tumours Undergoing Preoperative (SETUP) NAC study. We found 9 significantly differentially methylated regions (DMRs) at diagnosis which were associated with response to NAC. We show that 4 of these DMRs are associated with TNBC overall survival (P < 0.05). Our results highlight the potential of DNA methylation biomarkers for predicting NAC response in TNBC.

Keywords: DNA methylation; Epigenetics; Methylome; Neoadjuvant chemotherapy; Triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers, Pharmacological / analysis*
Biomarkers, Tumor / analysis*
Biomarkers, Tumor / genetics
DNA Methylation / genetics
Female
Humans
Middle Aged
Neoadjuvant Therapy / methods
Neoadjuvant Therapy / standards*
Neoadjuvant Therapy / statistics & numerical data
Prognosis
Proportional Hazards Models
Triple Negative Breast Neoplasms / drug therapy*
Triple Negative Breast Neoplasms / etiology

Substances

Biomarkers, Pharmacological
Biomarkers, Tumor

Abstract

Publication types

MeSH terms

Substances

Grants and funding