Avtor/Urednik		Ravnik-Glavač, Metka; Potočnik, Uroš; Glavač, Damjan
Naslov		Molecular genetic approaches for screening of hereditary non-polyposis colorectal cancer
Tip		članek
Vir		In: Vizjak A, Ferluga D, Bussolati G, editors. Update in pathology. Proceedings of the 19th European congress of pathology: nephropathology pre-congress meeting advances in nephrology, pulmonary pathology pre-congress meeting; 2003 Sep 6-11; Ljubljana. Ljubljana: Faculty of medicine,
Leto izdaje		2003
Obseg		str. 214-6
Jezik		eng
Abstrakt		The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC) is the most common autosomal dominant inherited predisposition for colorectal cancer (CRC), accounting for 1-2% of all bowel cancer. Usual way to diagnose HNPCC is by a family history consistent with the dis ease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II). The main molecular cause of HNPCC is constitutional mutation in one of the mismatch repair (MMR) genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is pres- ent in about 90% of cancers of HNPCC patients. However of all MSI colorectal cancers 80-90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSI-L, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and manage ment of colorectal cancer. Some studies have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. This approach enables that the disease in obligate carriers is detected in earlier stages what greatly decreases cost for medical treatment and most importantly decreases mortality.
Deskriptorji		COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS MICROSATELLITE REPEATS