Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

David R. Goudie, Mariella D'Alessandro, Barry Merriman, Hane Lee, Ildikó Szeverényi, Stuart Avery, Brian D. O'Connor, Stanley F. Nelson, Stephanie E. Coats, Arlene Stewart, Lesley Christie, Gabriella Pichert, Jean Friedel, Ian Hayes, Nigel Burrows, Sean Whittaker, Anne Marie Gerdes, Sigurd Broesby-Olsen, Malcolm A. Ferguson-Smith, Chandra VermaDeclan P. Lunny, Bruno Reversade, E. Birgitte Lane

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinomaĝ€"like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars. High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndromegrelated disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer. © 2011 Nature America, Inc. All rights reserved.
Original languageEnglish (US)
Pages (from-to)365-371
Number of pages7
JournalNature Genetics
Volume43
Issue number4
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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