Couvé-Privat Sophie, Bouadjar Bakar, Avril Marie Françoise, Sarasin Alain, Daya-Grosjean Leela
Laboratory of Genetic Instability and Cancer, UPR2169 CNRS, Institut André Lwoff, 94801 Villejuif, France.
Cancer Res. 2002 Dec 15;62(24):7186-9.
The Sonic hedgehog (SHH) pathway is implicated in the etiology of the most common human cancer in Caucasians, the basal cell carcinoma (BCC). Mutations in the receptor of SHH, the patched gene, have been characterized in sporadic BCCs as well as those from patients with the rare genetic syndromes nevoid BCC and xeroderma pigmentosum (XP). To elucidate the role of UV in the deregulation of the SHH pathway, we analyzed for alterations of smoothened, a transmembrane signaling component regulated by patched, in BCCs and squamous cell carcinomas from UV hypersensitive XP patients. We find UV-specific smoothened mutations in 30% of XP BCCs, three times higher than those in sporadic Caucasian BCCs, confirming the high rate of UV-induced mutations in DNA repair-deficient XP patients. No alteration was found in XP squamous cell carcinomas, indicating the involvement of smoothened specifically in the development of BCC.
音猬因子（SHH）信号通路与白种人中最常见的人类癌症——基底细胞癌（BCC）的病因有关。SHH受体patched基因的突变已在散发性BCC以及患有罕见遗传性综合征——痣样基底细胞癌综合征和着色性干皮病（XP）患者的BCC中得到鉴定。为了阐明紫外线在SHH信号通路失调中的作用，我们分析了来自紫外线超敏XP患者的BCC和鳞状细胞癌中受patched调控的跨膜信号成分smoothened的改变。我们在30%的XP BCC中发现了紫外线特异性的smoothened突变，这一比例是散发性白种人BCC的三倍，证实了DNA修复缺陷的XP患者中紫外线诱导突变的高发生率。在XP鳞状细胞癌中未发现改变，表明smoothened特别参与了BCC的发生发展。
