T25 repeat in the 3' untranslated region of the CASP2 gene: a sensitive and specific marker for microsatellite instability in colorectal cancer.

摘要: DNA mismatch repair deficiency is observed in about 10% to 15% of all colorectal carcinomas and up 90% hereditary nonpolyposis cancer (HNPCC) patients. Tumors with defects acquire mutations short repetitive sequences, a phenomenon termed high-level microsatellite instability (MSI-H). The diagnosis MSI-H colon increasing relevance, because an independent prognostic factor cancer, seems influence the efficacy adjuvant chemotherapy, most important molecular screening tool identify HNPCC To make MSI typing feasible for routine pathology laboratory, highly reproducible cost effective laboratory tests are required. Here, we describe novel T25 mononucleotide marker 3'untranslated region CASP2 gene (CAT25) that displayed quasimonomorphic repeat pattern normal tissue 200 unrelated individuals Caucasian origin. In addition, CAT25 was monomorphic also tested donors African Asian origin (n = 102 n 79, respectively) thus differs from commonly used markers BAT25 BAT26. Without analysis corresponding tissue, correctly detected 56 57 specimens classified as by using standard National Cancer Institute/International Collaborative Group-HNPCC panel. Combined BAT26 multiplex PCR, samples were typed correctly. No false-positive results obtained 60 non-MSI-H control specimens. These data suggest should be included into panels testing allowing significant reduction complexity costs typing. Moreover, represents promising early detection germ line mutation carriers.