Germline mutations in the p73 gene do not predispose to familial prostate-brain cancer.
BACKGROUND
Analysis of high-risk prostate cancer (PC) families with at least one confirmed case of primary brain cancer (BC) has identified a region of genetic linkage on chromosome 1p36 termed CAPB. The p36 region of chromosome one has been reported to have frequent loss of heterozygosity (LOH) in brain and central nervous system (CNS) tumors and epidemiological studies have shown an increased relative risk of BC and tumors of the CNS in PC families. In 1997 a reported tumor suppressor with high homology to p53, termed p73, was mapped to the p36 region of chromosome one. Here, we examine the p73 gene as a potential candidate for CAPB.


METHODS
Ninety-four members from the 12 prostate-brain cancer families in which linkage was originally found were examined. The complete coding region and intron-exon boundaries of the p73 gene were analyzed for germline mutations by Single Stranded Conformational Polymorphism analysis (SSCP) and direct DNA sequencing.


RESULTS
Silent nucleotide substitutions only were detected within the coding regions of the gene in affected individuals. Nucleotide changes were detected in introns 1, 6, 8, 9, and 10, but all were located >or=16 base pairs from the splice site, and are thus unlikely to be deleterious mutations.


CONCLUSIONS
Germline mutations in the p73 gene are unlikely to be critical for inherited susceptibility to PC in this specified subset of families.
Peters
M A
MA
Division of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. mpeters@fhcrc.org
Janer
M
M
Kolb
S
S
Jarvik
G P
GP
Ostrander
E A
EA
Stanford
J L
JL
D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms / Q000235:genetics*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins