Maesawa C, Tamura G, Iwaya T, Ogasawara S, Ishida K, Sato N, Nishizuka S, Suzuki Y, Ikeda K, Aoki K, Saito K, Satodate R
Department of Pathology, Iwate Medical University School of Medicine, Monoka, Japan.
Genes Chromosomes Cancer. 1998 Mar;21(3):276-9.
The human homologue (PTCH) of the Drosophila segment polarity gene patched has recently been identified as a tumor-suppressor gene for nevoid basal cell carcinoma syndrome and for sporadic basal cell carcinomas of the skin. We analyzed 30 esophageal squamous cell carcinomas (ESCC) for intrageneic mutations of the PTCH gene by polymerase chain reaction-single-strand conformation polymorphism analysis followed by DNA sequencing. We identified two somatic PTCH mutations (7%) in 30 ESCC. These were a nonsense mutation (CAG to TAG at codon 361) in exon 8 and a missense mutation (CAG to CTG, Gln to Leu at codon 816) in exon 14. These tumors exhibited loss of heterozygosity at the polymorphic site of the PTCH gene. These results indicate that inactivation of the PTCH gene via a two-hit mechanism occurs in a subset of ESCC.
果蝇节段极性基因patched的人类同源物（PTCH）最近被确定为痣样基底细胞癌综合征和散发性皮肤基底细胞癌的肿瘤抑制基因。我们通过聚合酶链反应-单链构象多态性分析，随后进行DNA测序，分析了30例食管鳞状细胞癌（ESCC）中PTCH基因的基因内突变。我们在30例ESCC中鉴定出两个体细胞PTCH突变（7%）。这些突变分别是外显子8中的无义突变（密码子361处的CAG突变为TAG）和外显子14中的错义突变（密码子816处的CAG突变为CTG，谷氨酰胺突变为亮氨酸）。这些肿瘤在PTCH基因的多态性位点表现出杂合性缺失。这些结果表明，通过双打击机制使PTCH基因失活发生在一部分ESCC中。
