[Correlation of multiple gene changes with malignant phenotype of human gastric carcinoma].
OBJECTIVE
To investigate the alteration of oncogenes and tumor suppressor genes in gastric carcinogenesis.


METHODS
Southern blot, PCR/SSCP and DNA sequencing techniques were used in 33 gastric carcinomas to detect c-met, EGFR, c-erbB-2, AKT-2, c-Ha-ras, p53, p16 and nm23-H1, for the presence of amplification, deletion, mutation and rearrangement.


RESULTS
Most tumors (70%) haboured one or more altered genes. The number and type of gene alteration were different among individuals. Rearrangement of c-met was noted in 2/33 cases (6%), and amplification of c-met, c-erbB-2 and AKT-2 in 8/33 cases (24.2%), 1/33 cases (3%) and 2/18 cases (11%) respectively. Homozygous deletion of P16 was seen in 6/33 cases (18%). Loss of heterozygousity was also noted in nm23-H1 5/17 (29%) and p53 2/13 (16%). The mutation rate of p53 in exon 5-8 was 20/33 (61%). Point mutation of p53 was found at both early and advanced tumors. In contrast, amplification of oncogenes and loss of tumor suppressor genes were correlated with poorly differentiated and metastatic tumors.


CONCLUSIONS
Gastric carcinogenesis is a gradually developed process, results from sequencial alteration of multigenes. The malignant phenotype is associated with the degree of genetic abnormality.
Gao
C
C
School of Oncology, Beijing Medical University, Beijing Institute for Cancer Research.
Lu
Y
Y
D000230:Adenocarcinoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018734:Genes, erbB-2 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D013274:Stomach Neoplasms / Q000235:genetics*