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

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.

Differential whole-genome doubling based signatures for improvement on clinical outcomes and drug response in patients with breast cancer

“…Previous studies on molecular research in breast cancer have made significant contributions to clinical diagnosis and prognosis [ 18 ]. The heterogeneity of breast cancer subtypes has also been explained through various genomic events including large-scale somatic calls [ 19 ]. Moreover, anti-cancer peptides (ACPs), a new type of anti-cancer predictors, demonstrate the ability to inhibit the proliferation or migration of tumor cells while exhibiting a reduced propensity for inducing drug resistance [ 20 ].…”

“…McGranahan et al explored the evolutionary importance of WGD in cancer, and showed how this can be exploited to identify novel cancer genes [ 14 ]. Chia-Hsin Wu et al discovered the distribution patterns of WGD in triple-negative BRCA patients in the Taiwanese population (BCTW) and provided insights into the impact of WGD on the timing of tumor initiation and tumor maintenance events in BRCA subtypes [ 19 ]. However, Taylor's analysis exclusively anticipated the worse overall survival across various cancer types due to genomic doubling.…”

“…Collectively, there is still limited understanding regarding the exploration and elucidation of the role of WGD and its effects on other relevant molecular alterations in breast cancer prognosis and treatment response. The molecular characteristics of breast cancer driven by large-scale chromosomal abnormalities have not been thoroughly analyzed in terms of their impact on the development, prognosis, and treatment of breast cancer [ 19 ]. The understanding of how WGD contributes to shaping the patterns of genome characteristics for improving the prognosis of human breast cancers remains scarce.…”