1. ¹Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London, Queen Mary University of London, Whitechapel, London, UK
2. ²Genetic Skin Disease Group, St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College School of Medicine, St Thomas' Hospital, London, UK
3. ³Tumour Biology Laboratory, Cancer Research UK Clinical Centre, Queen Mary's School of Medicine and Dentistry, Barts and The London, John Vane Science Centre, London, UK
4. ⁴Department of Dermatology, University of Freiburg, Freiburg, Germany
5. ⁵Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
6. ⁶Dermatology Department, Hospital Universitario Autonoma de Nuevo Leon, Monterrey, Mexico

Correspondence: Dr Andrew P. South, Centre for Cutaneous Research, Bart's and The London, Queen Mary's School of Medicine and Dentistry, 4 Newark Street, London E1 2AT, UK. E-mail: a.p.south@qmul.ac.uk

Received 3 January 2007; Revised 2 March 2007; Accepted 23 March 2007; Published online 10 May 2007.

Abstract

Recent data suggest that individuals with recessive dystrophic epidermolysis bullosa (RDEB) only develop squamous-cell carcinoma (SCC) in the presence of the NC1 domain of type VII collagen. This conclusion was based on experimental work in which cryosections of SCCs from 10 people with RDEB all showed positive type VII collagen immunostaining and observations in a murine model of SCC development in which tumors only occurred using keratinocytes from RDEB subjects that expressed detectable levels of the NC1 domain of the type VII collagen protein. To assess whether the clinical interpretation was valid in another cohort of RDEB patients, we examined expression of type VII collagen in 17 SCC tumors excised from 11 patients. Indirect immunofluorescent staining of SCC cryosections and Western blotting of cultured keratinocyte lysates identified two RDEB individuals who did not express detectable levels of type VII collagen. Mutation analysis revealed that these two patients harbor compound heterozygous nonsense mutations within the region of the COL7A1 gene encoding the NC1 domain. These data suggest that individuals with RDEB can develop SCC regardless of type VII collagen expression and that additional factors have a role in explaining the high incidence of tumors complicating this genodermatosis.