Patients with recessive dystrophic epidermolysis bullosa develop squamous-cell carcinoma regardless of type VII collagen expression.
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.
Pourreyron
Celine
C
Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London, Queen Mary University of London, Whitechapel, London, UK.
Cox
Georgie
G
Mao
Xin
X
Volz
Andreas
A
Baksh
Nuzhat
N
Wong
Tracy
T
Fassihi
Hiva
H
Arita
Ken
K
O'Toole
Edel A
EA
Ocampo-Candiani
Jorge
J
Chen
Mei
M
Hart
Ian R
IR
Bruckner-Tuderman
Leena
L
Salas-Alanis
Julio C
JC
McGrath
John A
JA
Leigh
Irene M
IM
South
Andrew P
AP
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
D018389:Codon, Nonsense; D024143:Collagen Type VII; D004273:DNA, Neoplasm