Activating Smoothened mutations in sporadic basal-cell carcinoma

Jingwu Xie, Maximilien Murone, Shiuh Ming Luoh, Anne Ryan, Qimin Gu, Chaohui Zhang, Jeannette M. Bonifas, Ching Wan Lam, Mary Hynes, Audrey Goddard, Arnon Rosenthal, Ervin H. Epstein, Frederic J. De Sauvage

Research output: Contribution to journalArticle

978 Citations (Scopus)

Abstract

Basal-cell carcinomas (BCCs) are the commonest human cancer. Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities. The binding of Sonic hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTGH in basal-cell nevus syndrome. We report here the identification of activating somatic missense mutations in the SMO gene itself in sporadic BCCs from three patients. Mutant SMO, unlike wild type, can cooperate with adenovirus E1A to transform rat embryonic fibroblast cells in culture. Furthermore, skin abnormalities similar to BCCs developed in transgenic murine skin overexpressing mutant SMO. These findings support the role of SMO as a signalling component of the SHH-receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs.

Original languageEnglish (US)
Pages (from-to)90-92
Number of pages3
JournalNature
Volume391
Issue number6662
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Basal Cell Carcinoma
Basal Cell Nevus Syndrome
Mutation
Hedgehogs
Genes
Skin Abnormalities
Inborn Genetic Diseases
Missense Mutation
Oncogenes
Adenoviridae
Cell Culture Techniques
Fibroblasts
Skin
Neoplasms
Proteins

ASJC Scopus subject areas

  • General

Cite this

Xie, J., Murone, M., Luoh, S. M., Ryan, A., Gu, Q., Zhang, C., ... De Sauvage, F. J. (1998). Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature, 391(6662), 90-92. https://doi.org/10.1038/34201

Activating Smoothened mutations in sporadic basal-cell carcinoma. / Xie, Jingwu; Murone, Maximilien; Luoh, Shiuh Ming; Ryan, Anne; Gu, Qimin; Zhang, Chaohui; Bonifas, Jeannette M.; Lam, Ching Wan; Hynes, Mary; Goddard, Audrey; Rosenthal, Arnon; Epstein, Ervin H.; De Sauvage, Frederic J.

In: Nature, Vol. 391, No. 6662, 01.01.1998, p. 90-92.

Research output: Contribution to journalArticle

Xie, J, Murone, M, Luoh, SM, Ryan, A, Gu, Q, Zhang, C, Bonifas, JM, Lam, CW, Hynes, M, Goddard, A, Rosenthal, A, Epstein, EH & De Sauvage, FJ 1998, 'Activating Smoothened mutations in sporadic basal-cell carcinoma', Nature, vol. 391, no. 6662, pp. 90-92. https://doi.org/10.1038/34201
Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C et al. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998 Jan 1;391(6662):90-92. https://doi.org/10.1038/34201
Xie, Jingwu ; Murone, Maximilien ; Luoh, Shiuh Ming ; Ryan, Anne ; Gu, Qimin ; Zhang, Chaohui ; Bonifas, Jeannette M. ; Lam, Ching Wan ; Hynes, Mary ; Goddard, Audrey ; Rosenthal, Arnon ; Epstein, Ervin H. ; De Sauvage, Frederic J. / Activating Smoothened mutations in sporadic basal-cell carcinoma. In: Nature. 1998 ; Vol. 391, No. 6662. pp. 90-92.
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