Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma–like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars1,2. 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 syndrome–related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer.
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This work was supported by Cancer Research UK (grants C26/A4049 to E.B.L. and D.R.G.; C26/A1461, C26/A6694 and C26/A11657 to E.B.L.) and the Biomedical Research Council (A*STAR) of Singapore. We thank the University of California Los Angeles Genomic Sequencing Center for providing access to next-generation sequencing, alignment and variant calling computational systems; F. Richards for tumor DNA; R. Barlow for subject referral; A. Cassidy for help with sequencing and the TaqMan assay; D. Baty for access to the resources of his laboratory and many individuals with MSSE for their help.
The authors declare no competing financial interests.
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Goudie, D., D'Alessandro, M., Merriman, B. et al. Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1. Nat Genet 43, 365–369 (2011). https://doi.org/10.1038/ng.780
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