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High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosum.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bodak, N. Queille, Sophie Avril, Marie Bouadjar, Bakar Drougard, C. Sarasin, Alain Daya-Grosjean, Leela |
| Copyright Year | 1999 |
| Abstract | Recently, hptc, a human gene homologous to the Drosophila segment polarity gene patched (ptc), has been implicated in the nevoid basal-cell carcinoma (BCC) syndrome, and somatic mutations of hptc also have been found in sporadic BCCs, the most frequent cancers found in the white population. We have analyzed the hptc gene, postulated to be a tumor suppressor gene, in 22 BCCs from patients with the hyperphotosensitive genodermatosis xeroderma pigmentosum (XP). Patients with XP are deficient in the repair of UV-induced DNA lesions and are characterized by their predisposition to cancers in sun-exposed skin. Analysis using PCR-single-strand conformation polymorphism of the hptc gene identified 19 alterations in 16 of 22 (73%) of the BCCs examined. Only two (11%) deletions of the hptc gene were found in XP BCCs compared with >30% rearrangement observed in non-XP sporadic BCCs, and 17 of 19 (89%) were base substitutions. Among the 17 base substitutions, 11 (65%) were CC --> TT tandem mutations, and 4 (23%) were C --> T substitutions, all targeted at bipyrimidine sites. Hence, a significantly higher number (15 of 19; 79%) of UV-specific alterations are seen in XP tumors, in contrast to non-XP sporadic BCCs. Interestingly, we have found that in 7 of 14 (50%) XP BCCs analyzed, both hptc and the tumor suppressor gene p53 are mutated. Not only have our data indicated the key role played by hptc in the development of BCCs, they also have substantiated the link between unrepaired UV-induced DNA lesions and skin carcinogenesis, as exemplified by the UV-specific alterations of different genes in the same tumors. |
| Starting Page | 013103 |
| Ending Page | 013103 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/96/9/5117.full.pdf |
| PubMed reference number | 10220428v1 |
| Volume Number | 96 |
| Issue Number | 9 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Carcinoma Clomiphene DNA Sequence Rearrangement Diploid Cell Malignant Neoplasms Mutation Nephroblastoma Patients Protein Patched Homolog 1, human Seventy Nine Skin Carcinogenesis Skin Diseases, Genetic Xeroderma Pigmentosum polarity |
| Content Type | Text |
| Resource Type | Article |
