The spectrum of TP53 mutations in bladder carcinoma

✍ Scribed by Magali P. Williamson; Patricia A. Elder; Margaret A. Knowles

• Book ID: 102845507
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 830 KB
• Volume: 9
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870090206

✦ Synopsis

The mutational spectrum for the TP53 gene was investigated in a large series of bladder tumors and bladder tumor cell lines. Tumors and cell lines were screened for the presence of TP53 point mutations by single-strand conformational polymorphism analysis followed by direct sequencing. Mutations were detected in I 6 of 88 (I 8%) tumors and 4 of I4 cell lines (28%). In total, twelve missense mutations, one nonsense mutation, three deletions, and two insertions were identified by direct sequencing. Of the thirteen point mutations sequenced, only one was a transition at a CpG site, whereas five G:C + T A transversions were found, suggesting a major role for exogenous mutagens in bladder tumorigenesis. Tumors were also examined for loss of heterozygosity (LOH) on chromosome arm 17p. LOH of one or more markers on 17p was detected in 31% of tumors. All eight tumors with a TP53 mutation from patients informative at TP53 had LOH, whereas nine tumors with LOH at TP53 did not have an identified mutation. Three tumors had LOH on I7p at sites distal t o the TP53 locus but retained both TP53 alleles, suggesting the involvement of another tumor suppressor gene on I7p in bladder tumorigenesis in some tumors. Genes Chrom Cancer 9:108-118 (1994).