Smyth I, Narang M A, Evans T, Heimann C, Nakamura Y, Chenevix-Trench G, Pietsch T, Wicking C, Wainwright B J
Centre for Molecular and Cellular Biology and Department of Biochemistry, Research Road, University of Queensland, Brisbane 4072, Australia.
Hum Mol Genet. 1999 Feb;8(2):291-7. doi: 10.1093/hmg/8.2.291.
Mutations of the human Patched gene ( PTCH ) have been identified in individuals with the nevoid basal cell carcinoma syndrome (NBCCS) as well as in sporadic basal cell carcinomas and medulloblastomas. We have isolated a homologue of this tumour suppressor gene and localized it to the short arm of chromosome 1 (1p32.1-32.3). Patched 2 ( PTCH2 ) comprises 22 coding exons and spans approximately 15 kb of genomic DNA. The gene encodes a 1203 amino acid putative transmembrane protein which is highly homologous to the PTCH product. We have characterized the genomic structure of PTCH2 and have used single-stranded conformational polymorphism analysis to search for mutations in PTCH2 in NBCCS patients, basal cell carcinomas and in medulloblastomas. To date, we have identified one truncating mutation in a medulloblastoma and a change in a splice donor site in a basal cell carcinoma, suggesting that the gene plays a role in the development of some tumours.
人类patched基因（PTCH）的突变已在痣样基底细胞癌综合征（NBCCS）患者以及散发性基底细胞癌和髓母细胞瘤中被发现。我们分离出了这个肿瘤抑制基因的一个同源物，并将其定位到1号染色体短臂（1p32.1 - 32.3）。patched 2（PTCH2）由22个编码外显子组成，跨越约15kb的基因组DNA。该基因编码一种1203个氨基酸的假定跨膜蛋白，与PTCH产物高度同源。我们已经对PTCH2的基因组结构进行了表征，并使用单链构象多态性分析来寻找NBCCS患者、基底细胞癌和髓母细胞瘤中PTCH2的突变。迄今为止，我们在一个髓母细胞瘤中鉴定出一个截短突变，在一个基底细胞癌中鉴定出一个剪接供体位点的改变，这表明该基因在某些肿瘤的发生发展中起作用。
