TY - JOUR
T1 - The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences
AU - Pan, Jia Wern
AU - Zabidi, Muhammad Mamduh Ahmad
AU - Ng, Pei Sze
AU - Meng, Mei Yee
AU - Hasan, Siti Norhidayu
AU - Sandey, Bethan
AU - Sammut, Stephen John
AU - Yip, Cheng Har
AU - Rajadurai, Pathmanathan
AU - Rueda, Oscar M.
AU - Caldas, Carlos
AU - Chin, Suet Feung
AU - Teo, Soo Hwang
N1 - Funding Information:
This project was funded by a research grant from the Newton-Ungku Omar Fund (MRC Ref: MR/P012442/1). Cancer Research Malaysia also receives charitable funding from the Scientex Foundation, Estée Lauder Companies, Yayasan Petronas, and Yayasan Sime Darby, which contributed to the funding of this study. This work (SFC, OMR, and CC) is also partly funded by Cancer Research UK (A16942). The authors would thank Dr. Tan Min Min for help with data curation, nurses, and staff who helped with sample collection, as well as Dr Saira Bahnu Mohamed Yousoof and all staff at the Subang Jaya Medical Centre Tissue Diagnostics laboratory for assistance with histopathological sample retrieval and processing. We also acknowledge the contribution of the Core Genomics Facility at the CRUK Cambridge Institute, where the sequencing work was conducted.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/12/22
Y1 - 2020/12/22
N2 - Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.
AB - Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.
UR - http://www.scopus.com/inward/record.url?scp=85097961579&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-20173-5
DO - 10.1038/s41467-020-20173-5
M3 - Article
C2 - 33353943
AN - SCOPUS:85097961579
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6433
ER -
