A gene-set approach to analyze copy number alterations in breast cancer

Genomic instability is one of the major driving forces of the accumulation of mutations during tumorigenesis. It leads to the complex mutational landscapes of cancer genomes, which include subtle sequence changes, large-scale chromosome translocations, gene amplifications, and alterations in chromosome number (1). These chromosomal aberrations may result in dysregulation of oncogenes and tumor suppressor genes and affect essential cellular functions, such as proliferation, apoptosis, and cell cycle regulation, leading to the transformation of normal cells into tumor cells (2). Distinct copy number alteration (CNA) patterns were reported to affect cancer-related genes in various types of cancers, suggesting the significance of CNAs in the diversified oncogenic mechanisms underlying cancers (3-6). Moreover, recent studies also showed the association between CNAs and patient survival (7-9). These findings have illuminated the potential role of CNAs as prognostic biomarkers in cancers