Expression of genes spanning a breast cancer susceptibility locus on 6q25. 1 is modulated by epigenetic modification

摘要: Single nucleotide polymorphisms within the region immediately upstream of the gene encoding ERα (ESR1) on 6q25.1, have been found to be associated with increased risk of breast cancer1,2. Three genes within this region, CCDC170, RMND1 and C6ORF211 are co-expressed with ESR1 in oestrogen receptor positive (ER+ve) breast cancers and CCDC170 expression is inversely associated with proliferation and recurrence free survival in a tamoxifen-treated patient cohort3. Epigenetic modification represents one potential mechanism through which expression of co-localised genes could be modulated. We investigated methylation and chromatin structure in the 6q25.1 using methylation sensitive sequencing, chromatin immunoprecipitation (ChIP) and chromatin confirmation capture (3C).Gene expression of ESR1, the three genes and alternative ESR1 mRNA isoforms were analysed in vitro using a panel of …