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.
Highlights
Whole-genome doubling (WGD) is an early macro-evolutionary event in tumorigenesis, involving the doubling of an entire chromosome complement
WGD potentially aggravates chromosomal instability (CIN) and accelerates cancer genome evolution, which has previously been shown to be associated with poor prognosis and drug resistance[3]
It can be hypothesized that WGD might explain distinct genomic complexity across breast cancer subtypes
Summary
Whole-genome doubling (WGD) is an early macro-evolutionary event in tumorigenesis, involving the doubling of an entire chromosome complement. Most molecular studies of breast cancer, which have contributed greatly toward identifying clinical subtype-specific genes, have been based on single-nucleotide variants (SNVs) and copy number alterations (CNAs)[2]. Such genetic variations offer a limited view of underlying breast cancer etiology as breast cancer is a multifactorial disease and variations such as these fail to provide a complete picture, and must be complemented by large-scale chromosomal abnormalities, which dominate the genomic landscape of cancer. HR hormone receptor, HER2 human epidermal growth factor 2 receptor, TNBC triple-negative breast cancer. *All values are presented as n (%) unless otherwise indicated
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