Analysis of the fragile histidine triad gene in primary gastric carcinomas and gastric carcinoma cell lines.
The FHIT (fragile histidine triad) gene has been isolated from the chromosome region 3p14.2, which includes the fragile site locus FRA3B and the breakpoint of the t(3;8) of familial renal carcinoma. FHIT has been suggested to be a candidate tumor suppressor gene for digestive tract carcinomas. To evaluate the significance of FHIT gene abnormalities in gastric carcinogenesis, we examined the allelic status and transcripts of the gene in 23 primary gastric carcinomas as well as 7 gastric carcinoma cell lines. Four of the seven (57%) cell lines exhibited homozygous deletions of variable sizes at 3p14.2 all of which included D3S1300, which is located close to, or within, FRA3B. However, only 2 of 16 (13%) informative cases showed loss of heterozygosity at D3S1300 in the primary tumors. Direct analysis by reverse transcriptase polymerase chain reaction failed to reveal abnormal transcripts, including exon skipping and sequence changes, in the primary tumors or in the cell lines without homozygous deletions. These results suggest that FHIT gene abnormalities are infrequent in primary gastric carcinomas and that the frequent homozygous deletions seen in cell lines might simply reflect the plasticity of the genome at FRA3B under culture conditions.
Tamura
G
G
Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
Sakata
K
K
Nishizuka
S
S
Maesawa
C
C
Suzuki
Y
Y
Iwaya
T
T
Terashima
M
M
Saito
K
K
Satodate
R
R
D017766:Acid Anhydride Hydrolases; D002872:Chromosome Deletion; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004252:DNA Mutational Analysis; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006801:Humans; D018895:Microsatellite Repeats; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase