Avtor/Urednik		Potočnik, Uroš
Naslov		Molekularno genetska analiza dednih in sporadičnih oblik kolorektalnega raka v slovenski populaciji
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Medicinska fakulteta
Leto izdaje		1998
Obseg		str. 97
Jezik		slo
Abstrakt		Colorectal cancer (CRC) is the third leading cancer and second leading cause of cancer mortality in the western world. There is over 800 new cases of CRC diagnosed in Slovenia annually. Besides environmental factors, notebly diet, there is a strong evidence for inherited predisposition for developing CRC in at least a subgroup of CRC. Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is the common form of hereditary CRC. In several epidemiological studies the incidence of HNPCC syndrome was estimated in-between 1 % -15% of all CRC (Lynch et al.,1993a). However HNPCC diagnosis is diffcult to perform since there are no clear phenotypical markers. The discovery of MicroSatellite Instability (MSI) and germline mutations in Mismatch Repair (MMR) genes in HNPCC patients enabled the molecular genetic approach for diagnosis of HNPCC syndrome. The aim of our study was to optimize strategy for presymptomatic diagnosis of HNPCC families based on molecular genetic approach and to study cancerogenesis of MSI tumors. Two hundred thirty randomly collected primary colorectal tumors were initially screened for microsatellite instability (MSI) with three highly informative microsatellite markers. Forty one (17.8%) tumors showed alterations in at least one marker. In further MSI analysis of these 41 MSI tumors with additional 9 markers, 21 tumors (9.1 % of 230 analyzed) exhibited MSI at more than 40% and these tumors were classified as high MSI tumors. Each of most informative microsatellite markers (BAT26 BAT25, BAT4O, D2S123 and D5S346) detected more than 90% of high MSI tumors. High MSI tumors were further analyzed with Polymerase Chain Reaction-Non Isotopic High Resolution Conformation Analysis (PCR-HRCA) for mutation in MMR genes. Sixteen (10 germline and 6 somatic) alterations in hMLH1 gene and 8 (6 germline and 2 somatic) alterations in hMSH2 gene were discovered. (Abstract truncated at 2000 characters)
Deskriptorji		COLORECTAL NEOPLASMS MUTATION MICROSATELLITE REPEATS COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS EXONS POLYMERASE CHAIN REACTION POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL BASE SEQUENCE