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

• Published in: Communications biology 2021-09, Vol.4 (1), p.1052-1052, Article 1052
• Main Authors: Wu, Chia-Hsin, Hsieh, Chia-Shan, Chang, Yo-Cheng, Huang, Chi-Cheng, Yeh, Hsien-Tang, Hou, Ming-Feng, Chung, Yuan-Chiang, Tu, Shih-Hsin, Chang, King-Jen, Chattopadhyay, Amrita, Lai, Liang-Chuan, Lu, Tzu-Pin, Li, Yung-Hua, Tsai, Mong-Hsun, Chuang, Eric Y.
• Format: Article
• Language: English
• Subjects: 45/23; 631/67/1347; 631/67/68; 631/67/69; Adult; Aged; Aged, 80 and over; Biology; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - classification; Breast Neoplasms - genetics; Chromosomes; ErbB-2 protein; Female; Genome, Human - genetics; Genomes; Genomic instability; Homologous recombination; Homologous Recombination - genetics; Humans; Life Sciences; Middle Aged; Mutation; Patients; Taiwan; Tumorigenesis; Tumors
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02597-x

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. Wu, Hsieh et al. analyze Taiwanese breast cancer patient samples using whole-exome sequencing to examine the heterogeneity and homogeneity in the timing and dependencies of somatic aberrations across disease subtypes. The authors focus on somatic alterations and related features that correlate with whole genome doubling, including homologous recombination deficiencies.