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Aberrant DNA methylation status of DNA repair genes in breast cancer treated with neoadjuvant chemotherapy
Author(s) -
Watanabe Yoshiyuki,
Maeda Ichiro,
Oikawa Ritsuko,
Wu Wenwen,
Tsuchiya Kyoko,
Miyoshi Yasuo,
Itoh Fumio,
Tsugawa Koichiro,
Ohta Tomohiko
Publication year - 2013
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12100
Subject(s) - rad51 , breast cancer , triple negative breast cancer , dna methylation , cancer research , biology , palb2 , methylation , carcinogenesis , dna repair , bisulfite sequencing , cancer , oncology , gene , mutation , germline mutation , medicine , genetics , gene expression
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 (p CR ), LBC with stable disease, triple‐negative breast cancer (TNBC) with p CR 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 p CR cases than in poor‐response cases in TNBC, that of RNF8 was significantly lower in p CR 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.