早发性家族性结直肠癌中的肿瘤抑制基因PTPRJ的生殖细胞系表观遗传沉默

Recently, we showed that 3′ deletion of the EPCAMgene leads to allele-specific epigeneticsilencing of the neighboring MSH2gene in Lynch syndrome patients.1 The underlying mechanism was found to constitute MSH2 promoter hypermethylation mediated by transcriptional read-through, thus providing an explanation of how colorectalcancer (CRC) susceptibility in these families could be inherited. Based on these findings and literature data, we hypothesized that constitutional genesilencing owing to a DNA copy number-based epimutation may act as a more general mechanism underlying CRC susceptibility. To test this hypothesis, we performed a genome-wide DNA copy number screen using Affymertix GeneChip