有哪些信誉好的足球投注网站molecular genetic analysis of 103 sporadic colorectal tumours in czech patients103年捷克零星的结直肠肿瘤的分子遗传分析病人.pdfVIP
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molecular genetic analysis of 103 sporadic colorectal tumours in czech patients103年捷克零星的结直肠肿瘤的分子遗传分析病人
Molecular Genetic Analysis of 103 Sporadic Colorectal Tumours in Czech Patients 1 1 1 2 3 3 Peter Vasovcak *, Kristyna Pavlikova , Zdenek Sedlacek , Petr Skapa , Martin Kouda , Jiri Hoch , Anna Krepelova1 1 Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic, 2 Department of Pathology and Molecular Medicine, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic, 3 Department of Surgery, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in Europe. To evaluate whether sporadic CRCs in Czech patients have specific mutational profiles we analysed somatic genetic changes in known CRC genes (APC, KRAS, TP53, CTNNB1, MUTYH and BRAF, loss of heterozygosity (LOH) at the APC locus, microsatellite instability (MSI), and methylation of the MLH1 promoter) in 103 tumours from 102 individuals. The most frequently mutated gene was APC (68.9% of tumours), followed by KRAS (31.1%), TP53 (27.2%), BRAF (8.7%) and CTNNB1 (1.9%). Heterozygous germline MUTYH mutations in 2 patients were unlikely to contribute to the development of their CRCs. LOH at the APC locus was found in 34.3% of tumours, MSI in 24.3% and MLH1 methylation in 12.7%. Seven tumours (6.9%) were without any changes in the genes tested. The analysis yielded several findings possibly specific for the Czech cohort. Somatic APC mutations did not cluster in the mutation cluster region (MCR). Tumours with MSI but no MLH1 methylation showed earlier onset and more severe mutational profiles
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