Περίληψη:
Breast cancer has distinct etiology, prognoses, and clinical outcomes at premenopausal ages. Determination of the frequency of germline and somatic mutations will refine our understanding of the genetic contribution to premenopausal breast cancer susceptibility. We applied a comprehensive next generation sequencing-based approach to analyze blood and/or tissue samples of 54 premenopausal breast cancer patients treated in our clinic. Genetic testing results were descriptively analyzed in correlation with clinicopathological data. In the present study, 42.5% of premenopausal breast cancer patients tested carried pathogenic mutations in cancer predisposition genes (CHEK2, BRCA1, TP53, and MUTYH). Germline variants of unknown/uncertain significance (VUSs) in eight different cancer susceptibility genes, namely BRCA1, BRCA2, CHEK2, RAD51C, RAD51D, ATM, BRIP1, and PMS2, were also identified in 14 premenopausal patients (35%). Of the breast tumors tested, 61.8% harbored pathogenic somatic variants in tumor suppressor genes (TP53, NF1, RB), genes involved in DNA repair (BRCA1, BRCA2, ATM, RAD50), cell proliferation (PTEN, PIK3C FGFR3, AKT1, ROS1, ERBB2, NOTCH1), and cell adhesion (CTNNB1). This descriptive study employs the powerful NGS technology to highlight the high frequency of premenopausal cases attributable to genetic predisposition. Mutation identification in a larger cohort may further ensure that these patients receive tailored treatment according to their menopausal status. © 2022 by the authors.
Συγγραφείς:
Zografos, E.
Andrikopoulou, A.
Papatheodoridi, A.M.
Kaparelou, M.
Bletsa, G.
Liontos, M.
Dimopoulos, M.-A.
Zagouri, F.
Λέξεις-κλειδιά:
adult; AKT1 gene; Article; ATM gene; breast cancer; BRIP1 gene; cancer susceptibility; CHEK2 gene; cohort analysis; CTNNB1 gene; descriptive research; female; FGFR3 gene; gene; gene mutation; genetic predisposition; germline mutation; high throughput sequencing; human; human tissue; major clinical study; middle aged; MUTYH gene; NF1 gene; NOTCH1 gene; oncogene; oncogene neu; PIK3C gene; PMS2 gene; premenopause; proto oncogene; PTEN gene; RAD50 gene; RAD51C gene; RAD51D gene; RB gene; retrospective study; ROS1 gene; somatic mutation; tumor suppressor gene; breast tumor; genetics; high throughput sequencing; mutation; pathology; procedures, oncoprotein; protein tyrosine kinase, Breast Neoplasms; Female; High-Throughput Nucleotide Sequencing; Humans; Mutation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins
