Correlation of multiple gene changes with malignant phenotype of human gastric carcinoma
Gao Chongfeng Lu Youyong (School of Oncology,Beijing Medical University ,,Beijing Institute for Cancer Research ,Beijing 100034.)
Objective To investigate the alteration of oncogenes and tumor suppressor genes in gastric carcino- genesis. 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 , p1 6 and nm23-H1 , for the presence of amplification , deletion , mutation and rearrangement . Resul ts Most tumors ( 7 0 % ) haboured one or more altered genes. The number and type of gene alteration were different among indi- viduals. 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. Homozy- gous deletion of P16 was seen in 6/33 cases (18% ). Loss of heterosygousity 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 mu- tation of p5 3 was found at both early and advanced tumocs. In contrast , amplification of oncogenes and loss of tumor suppressor genes were correlated with poorly differentiated and metastatic tumors. Cooclu- slons Gastric carcinogenesis is a gradually developed process , results from sequencial alteration of multigenes. The malignant phenotype is associated with the degree of genetic abnormality.