Author/Editor		Potočnik, U; Glavač, D; Golouh, R; Ravnik-Glavač, M
Title		Causes of microsatellite instability in colorectal tumors: implications for hereditary non-polyposis colorectal cancer screening
Type		članek
Source		Cancer Genet Cytogenet
Vol. and No.		Letnik 126, št. 2
Publication year		2001
Volume		str. 85-96
Language		eng
Abstract		Microsatellite instability (MSI) analysis was performed using a "reference panel" of microsatellite markers in 345 unselected primary colorectal cancers (CRC). Thirty-five (10%) tumors were classified as high MSI (MSI-H). We identified 6 (17%) MSI-H tumors with germline mutations in mismatch repair (MMR) genes (tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) syndrome) and 29 (83%) MSI-H tumors without germlin MMR mutations (sporadic MSI-H tumors). Hypermethylation of the hMLH1 promoter was found in 26/29 (90%) sporadic MSI-H tumors but only in 1/6 (17%) HNPCC tumors (P<.001). Somatic alterations were identified in both MMR genes in HNPCC tumors but mainly in the hMSH2 gene in sporadic MSI-H tumors. LOH at MMR loci was detected in 3/6 (50%) HNPCC tumors and in 4/26 (15%) informative sporadic MSI-H tumors. These results together indicate different mode of inactivation of MMR genes in sporadic MSI-H tumors versus MSI-H tumors in HNPCC patients. We therefore propose that MSI analysis of newly diagnosed primary CRC followed by methylation analysis of hMLH1 promoter in MSI-H tumors and mutational analysis of MMR genes in MSI-H tumors lacking hMLH1 promoter methylation might be an efficient molecular genetic approach for HNPCC screening.
Descriptors		COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS MASS SCREENING MICROSATELLITE REPEATS MIDDLE AGE AGED DNA METHYLATION GERM-LINE MUTATION MOLECULAR SEQUENCE DATA NEOPLASM PROTEINS PROMOTER REGIONS (GENETICS) PROTO-ONCOGENE PROTEINS