Segmental basal cell naevus syndrome caused by an activating mutation in smoothened

The British Journal of Dermatology
Z KhamaysiR Bergman

Abstract

Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS). Mutations in smoothened (SMO) encoding a receptor for sonic hedgehog have been reported in sporadic BCCs but not in BCNS. We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in three BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with the type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in increased SMO transactivating activity, and the patient responded to vismodegib therapy. Activating mutations in SMO may cause BCNS. The identification of a gain-of-function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumours, whether sporadic or inherited.

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Citations

Apr 8, 2017·American Journal of Medical Genetics. Part a·Kristen WigbyMarilyn C Jones
Sep 3, 2019·The British Journal of Dermatology·J E Mellerio
Sep 16, 2017·Current Opinion in Pediatrics·Andrew O M WilkieSteven A Wall
Apr 17, 2020·Experimental Dermatology·Amir Hossein SaeidianNeda Nikbakht
Mar 20, 2018·Frontiers in Pediatrics·Antonia ReimerCristina Has
Aug 8, 2020·International Journal of Molecular Sciences·Emi DikaMartina Lambertini
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Aug 11, 2021·The British Journal of Dermatology·B J A VerkouterenK Mosterd

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