PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study
Open Access
- 15 August 2006
- journal article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 95 (4), 548-553
- https://doi.org/10.1038/sj.bjc.6603303
Abstract
The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS) reported in various studies ranges from 40 to 80%. However, few studies have investigated the role of PTCH in clinical conditions suggesting an inherited predisposition to basal cell carcinoma (BCC), although it has been suggested that PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we therefore performed an exhaustive analysis of PTCH (mutations detection and deletion analysis) in 17 patients with the full complement of criteria for NBCCS (14 sporadic and three familial cases), and in 48 patients suspected of having a genetic predisposition to BCC (MBCC and/or age at diagnosis < or =40 years and/or familial BCC). Eleven new germline alterations of the PTCH gene were characterised in 12 out of 17 patients harbouring the full complement of criteria for the syndrome (70%). These were frameshift mutations in five patients, nonsense mutations in five patients, a small inframe deletion in one patient, and a large germline deletion in another patient. Only one missense mutation (G774R) was found, and this was in a patient affected with MBCC, but without any other NBCCS criterion. We therefore suggest that patients harbouring the full complement of NBCCS criteria should as a priority be screened for PTCH mutations by sequencing, followed by a deletion analysis if no mutation is detected. In other clinical situations that suggest genetic predisposition to BCC, germline mutations of PTCH are not common.Keywords
This publication has 31 references indexed in Scilit:
- DHPLC Analysis of patients with Nevoid Basal Cell Carcinoma Syndrome reveals novelPTCHmissense mutations in the sterol-sensing domainHuman Mutation, 2005
- PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancerBritish Journal of Dermatology, 2005
- Delineation of an interstitial 9q22 deletion in basal cell nevus syndromeAmerican Journal of Medical Genetics Part A, 2004
- Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndromeGenetics in Medicine, 2004
- Nevoid basal cell carcinoma (Gorlin) syndromeGenetics in Medicine, 2004
- Susceptibility to Basal Cell Carcinoma: Associations with PTCH PolymorphismsAnnals of Human Genetics, 2004
- PTCH polymorphism is associated with the rate of increase in basal cell carcinoma numbers during follow‐up: Preliminary data on the influence of an exon 12‐exon 23 haplotypeEnvironmental and Molecular Mutagenesis, 2004
- Gene quantification using real-time quantitative PCR: An emerging technology hits the mainstreamExperimental Hematology, 2002
- [A nevoid basal cell carcinoma syndrome with chromosomal aberration].2000
- Nevoid basal cell carcinoma syndrome. Clinical findings in 37 Italian affected individualsClinical Genetics, 1999