Alterations of Fas (Apo-1/CD95) Gene in Cutaneous Malignant Melanoma

• Published in: The American journal of pathology Vol. 154; no. 6; pp. 1785 - 1791
• Main Authors: Shin, Min Sun, Park, Won Sang, Kim, Su Young, Kim, Ho Sik, Kang, Seok Jin, Song, Kye Yong, Park, Jik Young, Dong, Seung Myung, Pi, Jae Ho, Oh, Ro Ra, Lee, Jung Young, Yoo, Nam Jin, Lee, Sug Hyung
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.06.1999; ASIP; American Society for Investigative Pathology
• Subjects: Alleles; Biological and medical sciences; Dermatology; DNA Mutational Analysis; fas Receptor - genetics; fas Receptor - metabolism; Heterozygote; Humans; Immunohistochemistry; Loss of Heterozygosity; Medical sciences; Melanoma - genetics; Melanoma - metabolism; Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Regular; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Tumors of the skin and soft tissue. Premalignant lesions; Human; Immunohistochemistry; Skin disease; Microdissection; Malignant tumor; Carcinogenesis; Single strand conformation polymorphism; Polymerase chain reaction; Pathology; Malignant melanoma; Loss of heterozygosity; Skin; Mutation; Molecular biology; Apoptosis
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)65434-X

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling. The key role of the Fas system in negative growth regulation has been studied mostly within the immune system, and somatic mutations of Fas gene in cancer patients have been described solely in lymphoid-lineage malignancies. However, many nonlymphoid tumor cells have been found to be resistant to Fas-mediated apoptosis, which suggests that Fas mutations, one of the possible mechanisms for Fas resistance, may be involved in the pathogenesis of nonlymphoid malignancies as well. In this study, we have analyzed the entire coding region and all splice sites of the Fas gene for the detection of the gene mutations in 44 human malignant melanomas in skin by polymerase chain reaction, single-strand conformation polymorphism, and DNA sequencing. Overall, 3 tumors (6.8%) were found to have the Fas mutations, which were all missense variants and identified in the cytoplasmic region (death domain) known to be involved in the transduction of an apoptotic signal. The data presented here suggest that somatic alterations of the Fas gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human malignant melanomas.