Digenic/multilocus aetiology of multiple self-healing squamous epithelioma (Ferguson-Smith disease): TGFBR1 and a second linked locus.

Multiple self-healing squamous epithelioma (MSSE) is a rare familial skin cancer in which multiple tumours resembling crateriform squamous carcinomas are locally invasive but regress spontaneously after several months, leaving deep disfiguring facial scars and shallower scars on the limbs. First identified in a number of Scottish families, the condition has since been reported more widely. We review here the investigations leading to the discovery of loss of function mutations in TGFBR1 that are responsible for the disease. Loss of heterozygosity in tumours reveals that TGFBR1 acts as a tumour suppressor gene. TGFBR1 was initially excluded as the MSSE gene because it lies outside an extensive chromosome 9 haplotype shared by Scottish families. MSSE can now be regarded as a digenic/multilocus disease in view of the evidence of a second linked locus necessary for pathogenesis located within the Scottish haplotype. This article is part of a Directed Issue entitled: Rare Cancers.