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(American Journal of Pathology. 1999;154:1785-1791.)
© 1999 American Society for Investigative Pathology

Regular Articles

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

Min Sun Shin^*, Won Sang Park^*§, Su Young Kim^*, Ho Sik Kim, Seok Jin Kang, Kye Yong Song^||, Jik Young Park^*, Seung Myung Dong^*, Jae Ho Pi^*, Ro Ra Oh^*, Jung Young Lee^*§, Nam Jin Yoo^*§ and Sug Hyung Lee^*§

From the Departments of Pathology,^*
Biochemistry,
and Clinical Pathology
and the Cancer Research Institute,^§
College of Medicine, The Catholic University of Korea, Seoul, Korea, and the Department of Pathology,^||
Chung Ang University College of Medicine, Seoul, Korea

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.

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