Alterations of oncogenes in metastatic tumours of human gastric carcinomas.

To determine whether alterations in oncogenes are associated with tumour progression and metastasis, DNAs from 32 metastatic tumour samples of different sites in 12 autopsy cases of gastric carcinomas were analysed for alterations of ERBB, ERBB2, HST1, INT2 and LMYC genes by Southern blot hybridisation. DNAs from 89 primary gastric carcinomas including 69 advanced carcinomas and 20 early carcinomas were also examined. In primary tumours, no amplification was detected in early carcinomas, while amplification of ERBB and ERBB2 genes was detected in one (1.4%) and four (5.8%) out of 69 advanced carcinomas, respectively. In metastatic tumours, amplification of ERBB gene was detected in three metastatic tumours (9.4%), and all of them had allelic deletion of the LMYC gene. Regardless of histological type, amplification of ERBB2 gene was detected in 8 metastatic tumours (25.0%), out of which three tumours had coamplification of HST1 and INT2 genes. The incidence of ERBB2 amplification in metastatic tumours was significantly higher than that in primary tumours. These results indicate that multi-alterations in oncogenes might occur during tumour progression and metastasis of human gastric carcinomas.