[Methylation of promoter region of RASSF1A gene and frequencies of allelic imbalances in chromosome 3 critical regions are correlated with progression of clear cell renal cell carcinoma].
The short arm of chromosome 3 (3p) contains several critical regions harboring the set of genes with tumor suppressor activities. The RASSF1A gene (LUCA region, 3p21.31) shows various functions which can be associated with tumorigenesis. Among 3p genes this gene can be most frequently methylated in epithelial tumors of various locations. Here two independent methods (methyl-specific PCR and methyl-sensitive restriction analysis) were used to show significant correlation of methylation level of promoter region of this gene with grade and clinical stage of clear cell renal cell carcinoma (RCC) for the first time. Analysis of 23 polymorphic markers of 3p using the representative set of samples (80 cases RCC), described clinically and histological, permitted to reveal significant correlation between frequency of allelic alterations in some critical regions of 3p (LUCA and AP20) and RCC progression, as distinct from the whole 3p. These data suggest that methylation of promoter region of the RASSF1A gene is associated with RCC progression, and besides, structure-functional alterations in other 3p genes can be also related with RCC progression. In addition, significant correlation between RASSF1A methylation events and allelic losses in the close polymorphic marker was shown here, pointing to the role of "two hit" model for this tumor-suppressor gene inactivation in RCC.
Loginov
V I
VI
Khodyrev
D S
DS
Pronina
I V
IV
Kazubskaia
T P
TP
Ermilova
V D
VD
Gar'kavtseva
R F
RF
Braga
E A
EA
D022981:Allelic Imbalance; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002893:Chromosomes, Human, Pair 3 / Q000378:metabolism*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins