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 () and Frederic J. de Sauvage ()
Additional contact information
Jingwu Xie: San Francisco General Hospital
Maximilien Murone: Genentech Inc.
Shiuh-Ming Luoh: Genentech Inc.
Anne Ryan: Department of Pathology Genentech Inc.
Qimin Gu: Department of Molecular Biology Genentech Inc.
Chaohui Zhang: Genentech Inc.
Jeannette M. Bonifas: San Francisco General Hospital
Ching-Wan Lam: Prince of Wales Hospital
Mary Hynes: Genentech Inc.
Audrey Goddard: Department of Molecular Biology Genentech Inc.
Arnon Rosenthal: Genentech Inc.
Ervin H Epstein: San Francisco General Hospital
Frederic J. de Sauvage: Genentech Inc.

Nature, 1998, vol. 391, issue 6662, 90-92

Abstract: Abstract Basal-cell carcinomas (BCCs) are the commonest human cancer1. 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 abnormalities2,3,4,5,6,7. 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 protein8,9. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTCH 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.

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/34201 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:391:y:1998:i:6662:d:10.1038_34201

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/34201

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().