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Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and amplifications in breast cancer. Although such genetic changes may have phenotypic consequences, the identity of candidate gene(s) remains to be clearly defined. Pol β gene is localized to chromosome 8p12-p11 and encodes a key DNA base excision repair protein. Pol β may be a tumour suppressor and involved in breast cancer pathogenesis. We conducted the first and the largest study to comprehensively evaluate pol β in breast cancer. We investigated pol β gene copy number changes in two cohorts (n = 128 &n = 1952), pol β mRNA expression in two cohorts (n = 249 &n = 1952) and pol β protein expression in two cohorts (n = 1406 &n = 252). Artificial neural network analysis for pol β interacting genes was performed in 249 tumours. For mechanistic insights, pol β gene copy number changes, mRNA and protein levels were investigated together in 128 tumours and validated in 1952 tumours. Low pol β mRNA expression as well as low pol β protein expression was associated high grade, lymph node positivity, pleomorphism, triple negative, basal-like phenotypes and poor survival (ps < 0.001). In oestrogen receptor (ER) positive sub-group that received tamoxifen, low pol β protein remains associated with aggressive phenotype and poor survival (ps < 0.001). Artificial neural network analysis revealed ER as a top pol β interacting gene. Mechanistically, there was strong positive correlation between pol β gene copy number changes and pol β mRNA expression (p < 0.0000001) and between pol β mRNA and pol β protein expression (p < 0.0000001). This is the first study to provide evidence that pol β deficiency is linked to aggressive breast cancer and may have prognostic and predictive significance in patients.

Original publication




Journal article


Mol Oncol

Publication Date





520 - 532


Breast cancer, Pol β, Predictive factor, Prognostic factor, Breast, Breast Neoplasms, Cohort Studies, DNA Polymerase beta, Estrogen Receptor alpha, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Humans, Prognosis, RNA, Messenger