Mechanism of tumorigenesis of renal carcinomas associated with the constitutional chromosome 3;8 translocation.

摘要: PURPOSE Members of a family carrying constitutional balanced translocation [t(3;8) (p14;q24)] have high risk developing multiple, bilateral clear-cell renal carcinomas. Two genetic mechanisms carcinogenesis for this malignancy been proposed: (1) disruption gene at the breakpoint and (2) mutation von Hippel-Lindau tumor-suppressor 3p25. This study further evaluates role in etiology pathogenesis t(3;8)-associated METHODS new carcinomas were tested mutations by single-stranded conformational polymorphism analysis followed direct DNA sequencing, loss alleles on chromosomes 3p 8, methylation abnormalities first cloned exon gene. RESULTS A missense was found one two would produce stop codon truncated protein. Both tumors showed derivative 8 chromosome. When these results combined with our previous studies, four carcinomas, which examined molecular changes, different somatic mutations. All from 3;8 translocated portion chromosome 3. CONCLUSIONS These support mechanism tumorigenesis (3;8) that involves both copies