Somatic Mutations of Fas (Apo-1/CD95) Gene in Cutaneous Squamous Cell Carcinoma Arising from a Burn Scar

Abstract

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling, and recent reports have suggested that defects within the Fas receptor pathway such as Fas mutation play an important part in the development and progression of human tumors. Burn scar-related squamous cell carcinoma of skin is a unique subtype of cutaneous squamous cell carcinoma, and tends to be more aggressive in nature than conventional squamous cell carcinoma. The molecular mechanisms underlying the development and progression of burn scar-related squamous cell carcinoma, however, are not clear. In this study, we analyzed the entire coding region and all splice sites of the Fas gene for the detection of the somatic mutations in a series of 50 conventional squamous 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-related 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 ligand-binding domain, another one was identified in the death domain known to 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-related squamous cell carcinomas have Fas gene mutations in important regions for the apoptosis function and suggest that these mutations might be involved in the pathogenesis of burn scar-related squamous cell carcinomas. In addition, our results provide an important clue to understanding the difference between burn scar-related squamous cell carcinoma and conventional squamous cell carcinoma at the molecular level.

Expression of Fas and Fas ligand in human gastric adenomas and intestinal-type carcinomas: correlation with proliferation and apoptosis

“…Recently, somatic mutations of the Fas gene have been demonstrated in a variety of human malignancies (including lymphomas [35][36][37]), as well as in various solid tumors (including gastric carcinoma [25][26][27][28]38]). Park et al [27] detected missense mutations in the death domain of the Fas gene in 5 (11.6%) of 43 gastric carcinomas.…”

“…Park et al [27] detected missense mutations in the death domain of the Fas gene in 5 (11.6%) of 43 gastric carcinomas. In the present study, we investigated whether there were alterations in the Fas gene in seven gastric carcinoma cell lines, 20 gastric adenomas, and 30 gastric carcinomas, targeting exons 6 and 9, which encode the transmembrane domain and the death domain of Fas, respectively [39,40], and which are known to show mutations more frequently than other exons [25][26][27][28]38]. However, no mutations were detected in any samples, except for one gastric carcinoma that showed a silent mutation (Leu-to-Leu).…”

“…PCR primers were synthesized based on the Fas DNA sequences in exons 6 and 9, which encode the transmembrane domain and death domain, respectively. The sequences of the primer pairs were: 5Ј-tttcatataatatgccaatgttcc-3Ј and 5Ј-cttcccccaag ttatttcaat-3Ј for Fas exon 6; 5Ј-tgctggagtcatgacactaagt-3Ј and 5Ј-caatgtgtcatacgcttctttc-3Ј for Fas exon 9A; 5Ј-taattggcatcaacttcat-3Ј and 5Ј-gaatttgttgtttttcactcta-3Ј for Fas exon 9B; and 5Ј-ggttttcactaatgggaatttcat-3Ј and 5Ј-cttcattgacaccattctttcg-3Ј for Fas exon 9C [25][26][27][28]. Exon 9 was divided into three fragments.…”

Proteomic Investigation of Human Burn Wounds by 2D-Difference Gel Electrophoresis and Mass Spectrometry

“…SCCA1 acts to protect UV-exposed (stressed) keratinocytes from apoptosis (34). SCCA-1 and 2 have been associated with several different forms of cancer, but never directly with the rare squamous cell carcinomas development in burn tissue (35,36). Thus this molecule is a newly discovered candidate protein in the burn wound.…”

A precancerous saree lesion: a rare occurrence

“…11 The more recent theories have included genetic postulations which involve the Human Leukocyte Antigen (HLA) DR4 and mutations in the p53 and/or the FAS genes. 12,13 This cancer is locally infiltrating and extensive metastasis at the time of diagnosis is uncommon.…”