RRC ID 38841
Author Tamura G, Sakata K, Nishizuka S, Maesawa C, Suzuki Y, Iwaya T, Terashima M, Saito K, Satodate R.
Title Inactivation of the E-cadherin gene in primary gastric carcinomas and gastric carcinoma cell lines.
Journal Jpn J Cancer Res
Abstract We investigated the E (epithelial)-cadherin gene for mutations and loss of heterozygosity (LOH) in 24 primary gastric carcinomas (12 differentiated and 12 undifferentiated types, including 3 signet-ring cell carcinomas), as well as 4 gastric carcinoma cell lines of the undifferentiated type (MKN-45, GCIY, HGC-27 and GT3TKB). We utilized PCR-SSCP and RT-PCR followed by direct sequencing to detect gene mutations and skipped exons, and RT-PCR-SSCP to examine LOH. In primary carcinomas, gene mutations or skipped exons were detected in 4 of 9 (44%) undifferentiated carcinomas of the scattered type, including 2 signet-ring cell carcinomas, and in none of the 3 undifferentiated carcinomas of the adherent type and 12 differentiated carcinomas. Demonstrated mutations of the E-cadherin gene included an 18 bp deletion (codon 418-423) and a 3 bp deletion (codon 400, calcium-binding domain), both located in exon 9. Skipping of exon 9 with a 1 bp insertion at codon 337, and skipping of exon 8 with a 1 bp deletion at codon 336, also were detected. LOH was confirmed in all of the carcinomas in which gene mutations or skipped exons (3/3 informative cases) were demonstrated. The MKN-45 cell line exhibited an 18 bp deletion at the exon 6-intron 6 boundary with loss of the wild-type allele, and 2 of the remaining 3 cell lines (HGC-27 and GT3TKB) had lost expression without detectable structural alteration of the E-cadherin gene. These data provide support for classic two-hit inactivation of the E-cadherin gene in a high percentage of undifferentiated carcinomas of the scattered type.
Volume 87(11)
Pages 1153-9
Published 1996-11-1
DOI 10.1111/j.1349-7006.1996.tb03125.x
PII S0910505097871025
PMID 9045944
PMC PMC5921011
MeSH Alleles Base Sequence Cadherins / biosynthesis* Cadherins / genetics* Carcinoma / genetics* Carcinoma / metabolism* Exons Gene Deletion Gene Expression Regulation, Neoplastic* Heterozygote Humans Molecular Sequence Data Mutation Polymerase Chain Reaction Polymorphism, Genetic Polymorphism, Single-Stranded Conformational Stomach Neoplasms / genetics* Stomach Neoplasms / metabolism* Transcription, Genetic Tumor Cells, Cultured
Times Cited 100
Human and Animal Cells