title: Aberrant DNA methylation status of DNA repair genes in breast cancer treated with neoadjuvant chemotherapy.
abstract: Dysregulation of homologous recombination (HR) DNA repair has been implicated in breast carcinogenesis and chemosensitivity. Here, we investigated the methylation status of sixteen HR genes and analyzed their association with tumor subtypes and responses to neoadjuvant chemotherapy. Core specimens were obtained before neoadjuvant chemotherapy from sixty cases of primary breast cancer of the following four subgroups: luminal breast cancer (LBC) with pathological complete response (pCR), LBC with stable disease, triple-negative breast cancer (TNBC) with pCR and TNBC with poor response. The aberrant DNA methylation status of the following HR related-genes was analyzed using bisulfite-pyrosequencing: BRCA1, BRCA2, BARD1, MDC1, RNF8, RNF168, UBC13, ABRA1, PALB2, RAD50, RAD51, RAD51C, MRE11, NBS1, CtIP and ATM. Among the genes analyzed, only the incidence of BRCA1 and RNF8 methylation was significantly higher in TNBC than that in LBC. Whereas the incidence of BRCA1 methylation was tended to be higher in pCR cases than in poor-response cases in TNBC, that of RNF8 was significantly lower in pCR cases than in poor-response cases. Our results indicate that the methylation status of HR genes was not generally associated with TNBC subtype or chemosensitivity although hypermethylation of BRCA1 is associated with TNBC subtype and may impact chemosensitivity.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Maeda
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Oikawa
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wu
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Fumio
authors.initials: F
authors.lastname: Itoh
authors.forename: Ko-ichiro
authors.initials: K
authors.lastname: Tsugawa
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands; D003520:Cyclophosphamide / Q000008:administration & dosage; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics*; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D059765:Homologous Recombination; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D043823:Taxoids / Q000008:administration & dosage; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate