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 IDENTIFICATION OF A CANDIDATE GENE FOR BASAL CELL NEVUS SYNDROMEBasal cell carcinoma (BCC) is one of the most common human neoplasms. Nearly 750,000 new cases of BCC are diagnosed each year in the US alone. The majority of cases of BCC which arise sporadically are often found in the sun exposed areas of skin of older individuals. However, a form of BCC appears in an inherited form and is transmitted in an autosomal dominant fashion. This form of BCC appears, in large numbers, usually in the second decade of life. This form of skin cancer is also associated with other types of tumors such as medulloblastoma, meningioma, fibroma of the ovary, as well as cyst of the skin and the jaw, and developmental abnormalities such as rib and craniofacial alterations. Polydactyly, syndactyly and spina bifida are found at a lesser frequency. This constellation of abnormalities are collectively referred to as basal nevus syndrome. In the June 14, 96 issue of Science Johnson et al report that basal nevus syndrome and occasional cases of sporadic BCC are associated with mutations in the human homolog of the Drosophila patched (ptc) gene. The assembled 5.1 kilobases of contiguous sequence of the human PTC gene contained a 4.5-kb of open reading frame (ORF) and encoded a protein with 1447 amino-acids containing 12 hydrophobic membrane-spanning domains and two large hydrophilic extracellular loops. The predicted protein showed 96% and 40% amino-acid identity, respectively with the mouse and Drosophila genes. The human gene was mapped to chromosome 9, in close proximity of the meiotic marker D9S287 which lies between D9S196 and D9S176. These markers reside in the band 9q22.3. The nucleotide sequence of PTC is deposited in GenBank (accession number U59464). Two independent sequence changes were identified in the blood cells of individuals with basal nevus syndrome, one an insertion of 9 nucleotides (CCGAATATC) at nucleotide 2445 of the coding sequence and the other change was deletion of 11 nucleotides (TATCCAGCACT) in positions 2442 to 2452 of the coding sequence. The development of mutations in the PTC gene was less common in the sporadic form of BCC. In only one of 12 BCCs, a C to T transition in exon 3 at nucleotide 523 of the coding sequence was found. These findings provide a strong support that the mutations of PTC is implicated in the development of BCC in patients with basal nevus syndrome. In the vertebrates, various lines of evidence link the expression of ptc to the development of branchial arches, limbs, spinal cord and sclerotome. Therefore, the developmental abnormalities in patients with basal nevus syndrome may also be related to the aberrations in the PTC gene. REFERENCES: Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP: Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272, 1668-1671, 1996
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Gene Map Locus: 9q22.3 |
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