Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer

K. P.M. Suijkerbuijk, M. J. Fackler, S. Sukumar, C. H. Van gils, T. Van laar, E. Van der wall, M. Vooijs, P. J. Van Diest

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Promoter methylation is a common epigenetic mechanism to silence tumor suppressor genes during breast cancer development. We investigated whether BRCA1-associated breast tumors show cancer-predictive methylation patterns similar to those found in sporadic tumors. Patients and methods: Quantitative multiplex methylation-specific PCR of 11 genes involved in breast carcinogenesis (RARB, RASSF1, TWIST1, CCND2, ESR1, SCGB3A1, BRCA1, BRCA2, CDKN2A, APC, CDH1) was carried out on 32 BRCA1-associated and 46 sporadic breast carcinomas and on normal breast tissue from seven BRCA1 mutation carriers and 13 non-carriers. Results: The extent of cumulative methylation increased with age (P < 0.001). The median cumulative methylation index (CMI) of all studied genes was significantly higher in tumors (89) than in normal tissue (13, P < 0.001). The median CMI was significantly lower in BRCA1-associated (59) than in sporadic breast tumors (122, P = 0.001), in estrogen receptor (ER)-negative tumors (73) than in ER-positive tumors (122, P = 0.005) and in lymph node-negative (77) compared with lymph node-positive tumors (137, P = 0.007). In subgroup analysis, the effect of a BRCA1 germline mutation on methylation proved to be independent of ER status, lymph node status and age. Conclusions: These data indicate that BRCA1-associated breast cancers show less promoter methylation compared with sporadic breast carcinomas indicating a difference in disease etiology.

Original languageEnglish (US)
Pages (from-to)1870-1874
Number of pages5
JournalAnnals of Oncology
Volume19
Issue number11
DOIs
StatePublished - 2008

Keywords

  • BRCA1
  • Breast cancer
  • Hereditary
  • Methylation
  • QM-MSP

ASJC Scopus subject areas

  • Hematology
  • Oncology

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