Mutation and association analyses of the candidate genes ESR1, ESR2, MAX, PCNA, and KAT2A in patients with unexplained MSH2-deficient tumors Nils RahnerFelix F. BrockschmidtVerena SteinkePhilip KahlTim Becker • Hans F. A. VasenJuul T. WijnenCarli J. M. TopsElke Holinski-Feder • Marjolijn J. L. LigtenbergLiesbeth SpruijtHeike GorgensSusanne Stemmler • Matthias KloorWolfgang DietmaierThe Dutch Cancer Genetics Group • Johannes SchumacherMarkus M. NothenPeter Propping

Lynch syndrome (Hereditary non-polyposis colorectal cancer/HNPCC) is a cancer susceptibility syndrome which is caused by germline mutations in DNA mismatch repair (MMR) genes, in particular MLH1 and MSH2. A pathogenic germline mutation in the respective MMR gene is suggested by the finding of a loss of a mismatch repair protein in tumor tissue on immunohistochemical staining combined with an early age of onset and/or the familial occurrence of colorectal cancer. Pathogenic germline mutations are identifiable in around 60% of patients suspected of Lynch syndrome, depending on the familial occurrence. The aim of the present study was to identify novel susceptibility genes for Lynch syndrome. 64 Healthy controls and 64 Lynch syndrome patients with no pathogenic MSH2 mutation but a loss of MSH2 expression in their tumor tissue were screened for rare and disease causing germline mutations