Mutational analysis of Fas ligand gene in human non-Hodgkin lymphoma

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Abstract:

Kim HS, Lee SH, Lee JW, Soung YH, Lee JH, Park JY, Cho YG, Kim CJ, Kim SY, Lee YS, Park WS, Kim SH, Lee JY, Yoo NJ. Mutational analysis of Fas ligand gene in human non-Hodgkin lymphoma. APMIS 2003;111:490–6.

Among the systems triggering apoptosis, the Fas-Fas ligand (FasL) system is recognized as a major pathway for the induction of apoptosis in cells and tissues. Ligation of Fas by either an agonistic antibody or FasL transmits a ‘death signal’ to the target cell, potentially triggering apoptosis. Alterations of genes along the Fas-mediated apoptosis pathway have been reported in many human cancers. However, there have been no data regarding FasL gene mutations in human cancers. We hypothesized that FasL gene mutation might be involved in the development of non-Hodgkin lymphoma (NHL). In this study, we analyzed the entire coding region of the FasL gene for the detection of somatic mutations in a series of 111 NHLs and found that one tumor had a FasL gene mutation in the cytoplasmic domain. To evaluate the functional alterations of the mutant in apoptosis, we overexpressed the mutant in 293T cells, but couldn't find any significant loss of cell death compared to the wild-type FasL. Together, these data suggest that FasL is occasionally mutated in human NHL and that FasL mutations appear to play no role in the pathogenesis of the vast majority of NHLs.

Keywords: Fas ligand; apoptosis; mutation; non-Hodgkin lymphoma

Document Type: Research Article

Affiliations: 1: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea 2: Laboratory of Radiation Effect, Korea Cancer Center Hospital, Seoul, Korea

Publication date: April 1, 2003

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