title: Mutations of the p53 and PTCH gene in basal cell carcinomas: UV mutation signature and strand bias.
abstract: Mutations of p53 and PTCH gene, two candidate tumor suppressor genes for basal cell carcinoma (BCC), were screened in 15 cases of sporadic BCCs that developed in sun-exposed skin region in a Korean population. p53 and PTCH mutations were detected at a frequency of 33 and 40%, respectively, and the mutations were predominantly UV-signature transition, C-->T transitions at dipyrimidine sites and CC-->TT tandem mutations. In both genes, the most common mutations were missense mutations resulting in amino acid substitution, which is different than the results from Caucasian BCCs where mutations are frequently predicted to make truncated or absent proteins. All mutations, except for one, occurred on the nontranscribed strand where is little efficient removal of UV-induced pyrimidine dimers relative to the transcribed strand. Loss of heterozygocity (LOH) of 9q22 for PTCH loci was found in eight of 15 informative cases of BCCs (53%), but none of the cases were informative for LOH of 17p13 for p53 loci. Not only do our data indicate the key role played by p53 and PTCH in the development of BCCs, these findings also suggest that UVB may significantly contribute to BCC tumorigenesis. Moreover, molecular epidemiology composed of incidence of p53 and PTCH mutations, difference in the type of mutation and repair bias of UV-induced DNA lesions might affect the distinct features of BCCs between different racial population.
authors: Department of Dermatology, Holy Family Hospital, College of Medicine, The Catholic University of Korea, Wonmi-ku, Pucheon, Kyunggido, South Korea.
authors: Mi-Yeon
authors: MY
authors: Kim
authors: Hyun Jeong
authors: HJ
authors: Park
authors: Seung-Cheol
authors: SC
authors: Baek
authors: Dae Gyoo
authors: DG
authors: Byun
authors: Dong
authors: D
authors: Houh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D007723:Korea; D008565:Membrane Proteins / Q000235:genetics* / Q000528:radiation effects; D008875:Middle Aged; D020125:Mutation, Missense / Q000528:radiation effects; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D012878:Skin Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53