title: Patients with recessive dystrophic epidermolysis bullosa develop squamous-cell carcinoma regardless of type VII collagen expression.
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.
authors.affiliation: Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London, Queen Mary University of London, Whitechapel, London, UK.
authors.forename: Celine
authors.initials: C
authors.lastname: Pourreyron
authors.forename: Georgie
authors.initials: G
authors.lastname: Cox
authors.forename: Xin
authors.initials: X
authors.lastname: Mao
authors.forename: Andreas
authors.initials: A
authors.lastname: Volz
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Baksh
authors.forename: Tracy
authors.initials: T
authors.lastname: Wong
authors.forename: Hiva
authors.initials: H
authors.lastname: Fassihi
authors.forename: Ken
authors.initials: K
authors.lastname: Arita
authors.forename: Edel A
authors.initials: EA
authors.lastname: O'Toole
authors.forename: Jorge
authors.initials: J
authors.lastname: Ocampo-Candiani
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Ian R
authors.initials: IR
authors.lastname: Hart
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Julio C
authors.initials: JC
authors.lastname: Salas-Alanis
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Andrew P
authors.initials: AP
authors.lastname: South
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics; D024143:Collagen Type VII / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016108:Epidermolysis Bullosa Dystrophica / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D011905:Genes, ras / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D024143:Collagen Type VII; D004273:DNA, Neoplasm