کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10914674 | 1088805 | 2014 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
DNA polymerase β deficiency is linked to aggressive breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression in multiple cohorts
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 8, Issue 3, May 2014, Pages 520-532
Journal: Molecular Oncology - Volume 8, Issue 3, May 2014, Pages 520-532
نویسندگان
Tarek M.A. Abdel-Fatah, Roslin Russell, Devika Agarwal, Paul Moseley, Michael Ayotunde Abayomi, Christina Perry, Nada Albarakati, Graham Ball, Stephen Chan, Carlos Caldas, Ian O. Ellis, Srinivasan Madhusudan,