Determination of copy number variations and affected gene networks in breast cancer

Triple-negative breast cancer (TNBC) is a highly aggressive form characterized by limited therapeutic options and notable molecular diversity. The present study performed a genome-wide analysis of copy number variations (CNVs) using high-density microarrays in tumor tissue (TUM), adjacent non-tumor tissue (ADJ) and leukocytes (LEU) obtained from five patients with TNBC. The present study identified both unique and shared CNVs across tissue samples, including alterations in key chromosomal regions such as 1q23.3, 1q32.1 and 8q24.3, which harbor oncogenes such as MYC, myeloid cell leukemia 1 (MCL1) and BCL9. Losses in 6q25.2 affecting estrogen receptor 1 (ESR1) gene were also detected. CNVs were enriched in genes associated with Hallmarks of Cancer, with TUM samples showing profiles associated with 'proliferation', 'metastasis' and 'immune evasion', ADJ samples with 'growth suppression' and LEU samples with 'genomic instability'. Pathway enrichment analyses revealed disrupted functions in 'DNA repair', 'extracellular matrix organization' and 'TP53 signaling' in TUM. Notably, EGFR, excision repair cross-complementing group 4 (ERCC4) and heat shock protein 90 alpha family class B member 1 (HSP90AB1) genes emerged as potential central nodes in interaction networks and may serve as markers or therapeutic targets. To the best of our knowledge, the present study is the first CNV profiling study in TNBC in Mexican patients, highlighting the importance of including underrepresented populations in genomic research to uncover distinct molecular signatures and potential diagnostic or therapeutic avenues. Bioinformatically predicted molecular signatures of TNBC involve both common and distinct CNV-associated Hallmarks of Cancer genes, which represent candidates for screening as potential TNBC biomarkers.