Avtor/Urednik		Hudler, Petra
Naslov		Analiza mutacij v popravljalnem genu hMLH1 pri slovenskih bolnikih z rakom želodca
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Mediciska fakulteta
Leto izdaje		2002
Obseg		str. 97
Jezik		slo
Abstrakt		Gastric cancer is one of the most common malignancy in Slovenia. According to data from "Cancer Registry for 1997" it is the fourth or seventh cause of cancer death for men and women, respectively. Lauren divided gastric carcinomas into intestinal (well differentiated) and diffuse (poorly differentiated) types. Advances in the field of molecular biology show that the particular combination of multiple gene changes found in gastric cancer differs depending on the two histological types, strongly indicating that different genetic pathways may exist for these two types. Alterations in the structure and function of oncogenes and tumor suppressor genes, as well as genetic instabillity are responsible for carcinogenesis of intestinal and diffuse gastric cancers. Errors in replication at microsatellites are seen in 23 to 64% of poorly differentiated carcinomas and 17 to 41% of intestinal-type cancers. Several studies showed that microsatellite instability (MSI) is one of the earliest changes in tumor progression. It is often caused by genetic and epigenetic changes in mismatch repair genes (MMR genes). Microsatellite mutator phenotype is the cause of many somatic frameshift and point mutations in non-coding repetitive sequences and coding regions associated with cell proliferation and apoptosis. Genetic mutations in hMLHI and transcriptional silencing of its promoter by hypermethylation lead to inactivation of mismatch repair system. Identification of pathogenic mutations in hMLHl might have implications for treatment of the disease. Some of the studies showed that loss of MMR function in cells demonstrates reduced responsiveness to specific drugs. MMR proteins are implicated in response to DNA damage and contribute to activation of apoptotic response. (Abstract truncated at 2000 characters).
Deskriptorji		STOMACH NEOPLASMS MUTATION EXONS INTRONS PROMOTER REGIONS (GENETICS) MICROSATELLITE REPEATS POLYMERASE CHAIN REACTION POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL BASE SEQUENCE DNA METHYLATION