A third Wilms' tumor locus on chromosome 16q

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Loss of heterozygosity (LOH) studies identify chromosomal regions frequently deleted in tumors, suggesting the presence of tumor suppressor genes.
• Wilms' tumorigenesis has been linked to WT1 gene on chromosome 11p13 and other genes on 11p15.
• Evidence suggests additional chromosomal sites, beyond chromosome 11, are involved in Wilms' tumor development.

Purpose of the Study:

• To screen 33 autosomal arms for allele loss in Wilms' tumors to identify novel tumor suppressor gene locations.
• To investigate the significance of allele loss on chromosome 16q in Wilms' tumorigenesis.
• To determine the parental origin of lost chromosome 16q alleles.

Main Methods:

• Loss of heterozygosity analysis was performed on 33 autosomal arms across a series of Wilms' tumors.
• Allele loss frequencies were calculated for specific chromosomal regions, particularly chromosome 11p and 16q.
• Parental origin analysis of lost chromosome 16q alleles was conducted in sporadic tumors.

Main Results:

• Significant allele loss was observed on chromosome 11p (11 of 25 tumors) and chromosome 16q (9 of 45 tumors).
• The overall frequency of allele loss at other screened loci was low (9 of 426 informative loci).
• In sporadic tumors, chromosome 16q allele loss involved both paternal and maternal origins equally (4 of 8 tumors each).

Conclusions:

• Nonrandom losses of chromosome 11p and 16q alleles are implicated in Wilms' tumorigenesis.
• Chromosome 16q is identified as a potential location for a third tumor suppressor gene involved in Wilms' tumor.
• Unlike chromosome 11p, chromosome 16q tumor suppressor genes are affected by loss of either parental allele.