BRAF/KRASgene sequencing of sebaceous neoplasms after mismatch repair protein analysis

Sebaceous neoplasms are cutaneous markers for the autosomal-dominant Muir-Torre syndrome (MTS). This phenotypic variant of Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes. Microsatellite instability or loss of protein expression suggests a mutation or promoter...

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Bibliographic Details
Published in:Human pathology 2014-06, Vol.45 (6), p.1213
Main Authors: Cornejo, Kristine M, Hutchinson, Lloyd, Deng, April, Tomaszewicz, Keith, Welch, Matthew, Lyle, Stephen, Dresser, Karen, Cosar, Ediz F
Format: Article
Language:English
Subjects:
Biopsy
Cloning
Deoxyribonucleic acid
DNA
Genes
Genetic testing
Mutation
Protein expression
Proteins
Studies
Tumors
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Summary:Sebaceous neoplasms are cutaneous markers for the autosomal-dominant Muir-Torre syndrome (MTS). This phenotypic variant of Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes. Microsatellite instability or loss of protein expression suggests a mutation or promoter hypermethylation in 1 of the MMR genes.BRAFgene sequencing may help to distinguish between patients with sporadic and LS-associated colorectal carcinomas with loss of MLH1 expression. LS-associated carcinomas are virtually negative forBRAFmutations, but a subset harborsKRASmutations. The aim of our study was to test sebaceous neoplasms for V600EBRAForKRASmutations to determine if these mutations are associated with somatic or germline MMR defects, analogous to colorectal carcinomas. Over a 4-year period, 32 cases comprising 21 sebaceous adenomas, 3 sebaceomas, and 8 sebaceous carcinomas with sufficient material for testing were collected. MMR immunohistochemistry showed that 7 neoplasms had combined loss of MLH1-PMS2, 16 neoplasms had combined loss of MSH2-MSH6, 2 neoplasms had solitary loss of MSH6, and 7 sebaceous neoplasms had intact protein expression.BRAF/KRAStesting revealed all sebaceous neoplasms contained a wild-typeBRAFgene. Two (15%) of 13 patients with MTS were found to harbor aKRASmutation and loss of MLH1 expression. We conclude that a V600EBRAFmutation may not be helpful in distinguishing sporadic from MTS-associated sebaceous neoplasms. Further studies are needed to determine ifKRASmutations are restricted to patients with MTS or are also present in sporadic sebaceous neoplasms.
ISSN:0046-8177
1532-8392
DOI:10.1016/j.humpath.2014.02.001