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Segmental basal cell naevus syndrome caused by an activating mutation in smoothened
Author(s) -
Khamaysi Z.,
Bochner R.,
Indelman M.,
Magal L.,
AvitanHersh E.,
Sarig O.,
Sprecher E.,
Bergman R.
Publication year - 2016
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14425
Subject(s) - vismodegib , smoothened , hedgehog signaling pathway , ptch1 , basal cell carcinoma , patched , hedgehog , basal cell nevus syndrome , mutation , pathogenesis , biology , basal (medicine) , sonic hedgehog , cancer research , basal cell , genetics , medicine , pathology , immunology , endocrinology , signal transduction , gene , insulin
Summary Aberrant sonic hedgehog signalling, mostly due to PTCH 1 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 BCC s but not in BCNS . We report a case with multiple BCC s, 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 BCC s 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.