Genetic markers with high degrees of polymorphisms are of vital importance in the construction of high resolution (2-4 cM) linkage maps of human chromosomes as specified in the short-term goals of the Human Genome Initiative. In this paper, we report on molecular and genetic characterization and physical localization of 11 new multiallele restriction fragment length polymorphism markers on human chromosome 3p. Ten of these represent three- and four-allele polymorphisms of the base substitution type probably at two adjacent restriction sites. One has been identified as a novel mini-satellite sequence comprising a variable copy number tandem repeat array of a G/T-rich 79-bp sequence. This collection of multiallele polymorphic (PIC values: 0.40-0.60) markers should prove valuable and increase the resolution power of the available chromosome 3p genetic markers.

Alleles↗

PubMedDate not supplied

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

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

Carcinoma, Renal Cell↗