GENOME-WIDE METHYLATION ANALYSIS AND USE TO IDENTIFY GENES SPECIFIC TO BREAST CANCER HORMONE RECEPTOR STATUS AND RISK OF RECURRANCE

摘要

To better understand the biology of hormone receptor-positive and negative breast cancer and to identify methylated gene markers of disease progression, a genome-wide methylation array analysis was performed on 103 primary invasive breast cancers and 21 normal breast samples using the Illumina Infinium HumanMethylation27 array that queried 27,578 CpG loci. Forty CpG loci showed differential methylation specific to either ER-positive or ER-negative tumors. Each of the 40 ER-subtype-specific loci was validated in silico using an independent, publicly available methylome dataset from The Cancer Genome Atlas (TCGA). In addition, 100 methylated CpG loci were identified that were significantly associated with disease progression. Arrays containing the ER-subtype-specific loci and their use in methods of diagnosis and treatment of breast cancer are provided.

主权项

1. An array of oligonucleotide probes for identifying methylated target DNA genes in a sample, comprising one or more oligonucleotide probes that each selectively bind methylated loci in a target DNA gene and a platform; wherein the probes are immobilized on the platform; and wherein at least one or more probes selectively bind methylated target DNA genes selected from the group consisting of ACADL, ADAMTSL1, ARFGAP3, B3GAT1, CDCA7, FAM78A, FAM89A, FLJ31951 (RNF145), FLJ34922 (SLFN11), GAS6, HAAO, HEY2, HOXB9, ITGA11, NETO, PROX1, PSAT1, RECK, SMOC1, SND1, TNFSF9, ADHFE1, DYNLRB2, HSD17B8, PDXK, PISD and WNK4.