Frequent activating HRAS mutations in trichilemmoma. (30th September 2014)

• Record Type: Journal Article
• Authors: Tsai, J.‐H.; Huang, W.‐C.; Jhuang, J.‐Y.; Jeng, Y.‐M.; Cheng, M.‐L.; Chiu, H.‐Y.; Kuo, K.‐T.; Liau, J.‐Y.
• Is Part Of: British journal of dermatology. Volume 171:Number 5(2014:Nov.)
• Page Start: 1073
• Page End: 1077
• Publication Date: 2014-09-30
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.13143
• Languages: English
• ISSNs: 0007-0963

Abstract

<abstract abstract-type="main" id="bjd13143-abs-0001"> <title>Summary</title> <sec id="bjd13143-sec-0001" sec-type="section"> <title>Background</title> <p>Trichilemmoma is a benign follicular epithelial tumour exhibiting outer root sheath differentiation. It is associated with Cowden syndrome and naevus sebaceus (NS), but the pathogenesis of sporadic tumours is poorly understood. Recently, NS was found to be caused by postzygotic <italic>HRAS</italic> or <italic>KRAS</italic> mutations.</p> </sec> <sec id="bjd13143-sec-0002" sec-type="section"> <title>Objectives</title> <p>We sought to determine whether NS‐related and NS‐unrelated trichilemmomas harbour RAS mutations.</p> </sec> <sec id="bjd13143-sec-0003" sec-type="section"> <title>Methods</title> <p>Formalin‐fixed and paraffin‐embedded blocks of 12 NS‐related and 15 NS‐unrelated trichilemmomas from 26 individuals were retrieved and analysed to determine the presence of mutations in exons 1 and 2 of the <italic>HRAS</italic>, <italic> KRAS</italic> and <italic>NRAS</italic> genes by polymerase chain reaction and direct sequencing. Mutational hotspots of the <italic>FGFR3</italic> and <italic>PIK3CA</italic> genes were also analysed for NS‐unrelated cases.</p> </sec> <sec id="bjd13143-sec-0004" sec-type="section"> <title>Results</title> <p>Among the 27 cases, mutually exclusive <italic>HRAS</italic> c.37G>C and c.182A>G mutations were observed in 17 and three tumours, respectively. Of the 12 NS‐related tumours, 11 (92%) harboured the <italic>HRAS</italic> c.37G>C substitution. Of the 15 sporadic tumours, nine (60%) harboured <italic>HRAS</italic> mutations, including six c.37G>C and three c.182A>G. An <italic>HRAS</italic> c.182A>G mutation was observed only in sporadic tumours. No mutations were observed in the other genes that were tested.</p> </sec> <sec id="bjd13143-sec-0005" sec-type="section"> <title>Conclusions</title> <p>The high frequency of <italic>HRAS</italic> activating mutations, including the c.182A>G substitution, which was rather rare in NS, suggests that most trichilemmomas are authentic neoplasms.</p> </sec> </abstract>