E-cadherin gene mutations in signet ring cell carcinoma of the stomach.
To clarify the significance of E-cadherin gene alterations in the development of diffuse-type adenocarcinoma of the stomach, we analyzed mutations of the E-cadherin gene using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method followed by direct sequencing. Twenty-two signet ring cell carcinomas of the stomach (10 intramucosal and 12 advanced cancers) were examined. Genomic DNA was extracted separately from cancerous and non-cancerous tissues and PCR-SSCP analysis was performed on exons 5 to 9 and the adjacent 30- to 40-base-pair intron sequences of the E-cadherin gene. Mobility shifts were found in 2 of the 10 intramucosal cancers. In 2 of the 12 advanced cancers, abnormalities of the E-cadherin gene were observed in intramucosal lesions as well as in deeply invaded areas. These results indicated that E-cadherin gene mutations are an early event in the development of signet ring cell carcinoma of the stomach. Direct sequencing revealed that the locations of mutations of the E-cadherin gene included the branch point sequence in the intron which is responsible for RNA splicing. Reverse transcriptase-PCR demonstrated aberrant RNA splicing in a case with a branch point mutation, suggesting that branch point mutations play an important role in functional modifications of E-cadherin in signet ring cell carcinoma of the stomach.
Muta
H
H
Pathology Division, National Cancer Center Research Institute, Tokyo.
Noguchi
M
M
Kanai
Y
Y
Ochiai
A
A
Nawata
H
H
Hirohashi
S
S
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing; D012194:RNA-Directed DNA Polymerase; D013274:Stomach Neoplasms / Q000235:genetics*
D015820:Cadherins; D012194:RNA-Directed DNA Polymerase