Sh. Lee et al., Somatic mutations of Fas (Apo-1/CD95) gene in cutaneous squamous cell carcinoma arising from a burn scar, J INVES DER, 114(1), 2000, pp. 122-126
Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signalin
g, and recent reports have suggested that defects within the Fas receptor p
athway such as Fas mutation play an important part in the development and p
rogression of human tumors. Burn scar-related squamous cell carcinoma of sk
in is a unique subtype of cutaneous squamous cell carcinoma, and tends to b
e more aggressive in nature than conventional squamous cell carcinoma. The
molecular mechanisms underlying the development and progression of burn sca
r-related squamous cell carcinoma, however, are not clear. In this study, w
e analyzed the entire coding region and all splice sites of the Fas gene fo
r the detection of the somatic mutations in a series of 50 conventional squ
amous cell carcinomas and 21 burn scar-related squamous cell carcinomas by
polymerase chain reaction, single strand conformation polymorphism, and DNA
sequencing. We detected mis-sense mutations in three of 21 burn scar-relat
ed squamous cell carcinomas (14.3%), whereas no mutation was detected in 50
conventional squamous cell carcinomas. Of the three Fas mutations detected
in the burn scar-related squamous cell carcinomas, one was found in Fas li
gand-binding domain, another one was identified in the death domain known t
o be involved in the transduction of an apoptotic signal, and the other one
was found in the transmembrane domain. Our data show that some burn scar-r
elated squamous cell carcinomas have Fas gene mutations in important region
s for the apoptosis function and suggest that these mutations might be invo
lved in the pathogenesis of burn scar-related squamous cell carcinomas. In
addition, our results provide an important clue to understanding the differ
ence between burn scar-related squamous cell carcinoma and conventional squ
amous cell carcinoma at the molecular level.