Figure 2: Expression and methylation analyses at the 17q21.31 ovarian cancer susceptibility locus.

(a) Genomic map and LD structure. The location and approximate size of 17 known protein-coding genes (grey) and one microRNA (blue) in the region are shown relative to the location of rs12942666. Orange indicates the location of the inversion polymorphism, and green indicates the region outside the inversion. (b) Gene expression (EOC and normal cell lines). Gene expression analysis in epithelial ovarian cancer (EOC) cell lines (T; n=51) compared with normal ovarian surface epithelial cells (OSECs) and fallopian tube secretory epithelial cells (FTSECs) (N; n=73) (*P<0.05, **P<0.01, ***P<0.001). (c) Gene expression (primary EOCs and normal tissue). Boxplots of The Cancer Genome Atlas (TCGA) Affymetrix U133A-array-based gene expression in primary high-grade serous ovarian tumours (T; n=568) and normal fallopian tube tissues (N; n=8). Where data were not available in TCGA, gene expression data from the Gene Expression Omnibus series GSE18520 data set containing 53 high-grade serous tumours and 10 normal ovarian tissues are shown (indicated by a red asterisk). (d) Methylation (primary tumours and normal tissue). Methylation analysis of 106 high-grade serous ovarian tumours compared with normal ovarian tissues (n=7). Methylation data were generated for CpG site(s) associated with each gene using the Illumina 450 methylation array. Pairwise analysis of methylation for an individual CpG for each gene is based on the CpG with most significant inverse relationship to gene expression (that is, cis negative), for a subset of 43 tumours having available gene expression data. Statistically significant cis-negative probes are indicated by a red open circle. (e) eQTL analysis (OSECs/FTSECs). eQTL analysis comparing expression of each gene to genotype for the most statistically significant SNP at 17q21.31 (rs12942666), for 73 normal OSEC/FTSEC lines. Data are presented as box plots comparing expression levels in cases carrying rare homozygotes/heterozygotes, with cases homozygous for the common allele. (f) eQTL analysis (primary EOCs). eQTL analysis comparing expression of each gene by genotype using level 3 gene expression profiling data from Agilent 244K custom arrays and level 2 genotype data from the Illumina 1M-Duo BeadChip for 568 high-grade serous ovarian cancer patients from TCGA. In all panels *P<0.05, **P<0.01, *** P<0.001. Grey X’s indicate data not available. Here, genotype data for rs2077606 is used (rather than rs12942666) because rs12942666 was not genotyped in the TCGA data set. (g) Methylation quantitative trait locus (mQTL) analysis (primary EOCs). mQTL analysis showing methylation status in 227 high-grade serous EOCs relative to rs12942666 genotype.