Abstract
It is now believed that genes regulating apoptosis are also important
variables in cancer development. Fas, a transmembrane protein of
the tumour necrosis factor receptor family, is a key molecule for
cell death signalling. The mutation of the primary structure of the
Fas gene might also be one of the possible mechanisms that disrupt
Fas-mediated apoptosis in tumour cells. The purpose of this study
was to determine whether somatic mutation of the Fas gene could be
involved in the tumourigenesis of gastric cancer. Polymerase chain
reaction (PCR)-based loss of heterozygosity (LOH) analysis with two
intragenic polymorphic markers, and mutation analysis for the entire
coding regions of the Fas gene were performed in 43 cases of gastric
cancer, using PCR-single-strand conformational polymorphism sequencing.
Five (11.6%) missense mutations were detected, only in the death
domain of the Fas gene. Although these mutations were observed only
in intestinal-type gastric cancers, there was no statistically significant
difference in the frequency of Fas mutation between intestinal- and
diffuse-type gastric cancer (p=0.068). Nine LOH out of 22 informative
cases were also detected with one or both markers (41%). Three of
them demonstrated a somatic mutation in the remaining allele, indicating
the inactivation of both alleles. These results suggest that genetic
alterations of the Fas gene may not only be limited to gastric cancer
cell protection through Fas resistance, but may also play an important
role in tumour promotion and/or progression in a subset of gastric
cancer.
- adenocarcinoma,_genetics/pathology
- adult
- aged
- aged,_80_and_over
- alleles
- antigens,_cd95,_genetics
- apoptosis,_genetics
- female
- genetic_markers
- humans
- loss_of_heterozygosity,_genetics
- male
- middle_aged
- mutation,_missense,_genetics
- polymerase_chain_reaction
- polymorphism,_single-stranded_conformational
- stomach_neoplasms,_genetics/pathology
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