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Vol 42(2008) N 6 p. 925-931; M.V. Nemtsova1,2, E.M. Paltseva1, A.Yu. Babayan1, D.S. Mihaylenko1,2, O.V. Babenko1,2, O.Yu. Samofalova3, P.V. Tsar'kov3, D.V. Zaletaev1,2 Molecular genetic analysis of the intratumoral clonal heterogeneity of colorectal adenocarcinomas 1Institute of Molecular Medicine, Sechenov Moscow Medical Academy, Moscow, 119991, Russia2Medical Genetic Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia 3Petrovsky Surgery Research Center, Russian Academy of Medical Sciences, Moscow, 119992, Russia Received - 2008-03-20; Accepted - 2008-06-17 Molecular genetic analysis of allelic deletions from the loci containing the tumor suppressor genes p16, p15, p19 (9p21), RB1 (13p14), PTEN (10q23), and TP53 (17p13); microsatellite instability; and activating mutations of K-RAS (codons 12 and 13) was performed in four different segments of sporadic colorectal cancer (CRC) in 11 patients. Intratumoral genetic heterogenity was detected in 9 out of 11 (81%) colorectal adenocarcinomas and was morphologically validated. Analysis of different segments of one tumor reported that not only intratumoral heterogeneity, but also the order of the appearance and distribution of molecular anomalies during tumorigenesis in sporadic CRC. K-RAS point mutations and anomalies of the p16-RB1-cyclin D pathway were assumed to occur prior to microsatellite instability and PTEN deletions during tumor progression. loss of heterozygosity, microsatellite instability, mutations, colorectal adenocarcinoma, clonal heterogeneity, intratumoral genetic heterogeneity |
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