Mutational analysis of Fas ligand gene in human non-Hodgkin lymphoma.
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.
Kim
Hong Sug
HS
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Lee
Sug Hyung
SH
Lee
Jong Woo
JW
Soung
Young Hwa
YH
Lee
Jong Heun
JH
Park
Jik Young
JY
Cho
Yong Gu
YG
Kim
Chang Jae
CJ
Kim
Su Young
SY
Lee
Yun-Sil
YS
Park
Won Sang
WS
Kim
Sang Ho
SH
Lee
Jung Young
JY
Yoo
Nam Jin
NJ
D017209:Apoptosis / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D053222:Fas Ligand Protein; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
D004273:DNA, Neoplasm; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins