Differential whole-genome doubling and homologous recombination deficiencies across breast cancer subtypes from the Taiwanese population

Chia-Hsin Wu; Chia-Shan Hsieh; Yo-Cheng Chang; Chi-Cheng Huang; Hsien-Tang Yeh; Ming-Feng Hou; Yuan-Chiang Chung; Shih-Hsin Tu; King-Jen Chang; Amrita Chattopadhyay; Liang-Chuan Lai; Tzu-Pin Lu; Yung-Hua Li; Mong-Hsun Tsai; Eric Y Chuang

doi:10.1038/s42003-021-02597-x

Differential whole-genome doubling and homologous recombination deficiencies across breast cancer subtypes from the Taiwanese population

Commun Biol. 2021 Sep 9;4(1):1052. doi: 10.1038/s42003-021-02597-x.

Authors

Chia-Hsin Wu^#¹, Chia-Shan Hsieh^#², Yo-Cheng Chang^#³, Chi-Cheng Huang⁴, Hsien-Tang Yeh⁵, Ming-Feng Hou⁶, Yuan-Chiang Chung⁷, Shih-Hsin Tu⁸, King-Jen Chang⁹, Amrita Chattopadhyay¹⁰, Liang-Chuan Lai¹¹, Tzu-Pin Lu¹², Yung-Hua Li¹, Mong-Hsun Tsai¹³, Eric Y Chuang^{14

15

16

17}

Affiliations

¹ Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
² Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan.
³ Yonglin Healthcare Foundation, New Taipei City, Taiwan.
⁴ Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ Department of Surgery, Lotung Poh-Ai Hospital, Yilan County, Taiwan.
⁶ Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ Department of Breast Surgery, Dajia Branch, Kuang Tien General Hospital, Taichung, Taiwan.
⁸ Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁹ Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
¹⁰ Bioinformatics and Biostatistics Core, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
¹¹ Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹² Department of Public Health, National Taiwan University, Taipei, Taiwan.
¹³ Institute of Biotechnology, National Taiwan University, Taipei, Taiwan. motiont@gmail.com.
¹⁴ Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan. chuangey@ntu.edu.tw.
¹⁵ Bioinformatics and Biostatistics Core, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan. chuangey@ntu.edu.tw.
¹⁶ Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan. chuangey@ntu.edu.tw.
¹⁷ Master Program for Biomedical Engineering, China Medical University, Taichung, Taiwan. chuangey@ntu.edu.tw.

^# Contributed equally.

Abstract

Whole-genome doubling (WGD) is an early macro-evolutionary event in tumorigenesis, involving the doubling of an entire chromosome complement. However, its impact on breast cancer subtypes remains unclear. Here, we performed a comprehensive and quantitative analysis of WGD and its influence on breast cancer subtypes in patients from Taiwan and consequently highlight the genomic association between WGD and homologous recombination deficiency (HRD). A higher manifestation of WGD was reported in triple-negative breast cancer, conferring high chromosomal instability (CIN), while HER2 + tumors exhibited early WGD events, with widely varied CIN levels, compared to luminal-type tumors. An association of higher activity of de novo indel signature 2 with WGD and HRD in Taiwanese breast cancer patients was reported. A control test between WGD and pseudo non-WGD samples was further employed to support this finding. The study provides a better comprehension of tumorigenesis in breast cancer subtypes, thus assisting in personalized treatment.

Publication types

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

MeSH terms

Adult
Aged
Aged, 80 and over
Breast Neoplasms / classification
Breast Neoplasms / genetics*
Female
Genome, Human / genetics*
Homologous Recombination / genetics*
Humans
Middle Aged
Mutation
Taiwan