A “Two-in-One Hit” Model of Shortcut Carcinogenesis in MLH1 Lynch Syndrome Carriers

See editorial on page 20. Lynch Syndrome: A Single Hereditary Cancer Syndrome or Multiple Syndromes Defined by Different Mismatch Repair Genes?GastroenterologyVol. 165Issue 1PreviewLynch syndrome is the most common type of hereditary cancer syndrome, affecting 1 in 280–400 individuals.1–3 This predisposition to cancer is caused by inherited or germline pathogenic changes in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. In some cases, constitutional promoter methylation of MLH1 or MSH2 (secondary to an EPCAM 5′ deletion) is also identified.4 Despite the specific genetic alterations, patients with Lynch syndrome receive nearly identical clinical management in most countries. Full-Text PDF