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Alterations of oncogenes in metastatic tumours of human gastric carcinomas
T Tsujino1, K Yoshida, H Nakayama
1First Department of Pathology, Hiroshima University School of Medicine, Japan.
Abstract:
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.
Insights
Oncogene alterations, including ERBB2 amplification, are linked to gastric cancer progression and metastasis. These genetic changes may drive tumor advancement and spread in patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric carcinoma is a significant global health concern.
- Understanding oncogene alterations is crucial for elucidating tumor progression and metastasis.
Purpose of the Study:
- To investigate the association between oncogene alterations and tumor progression in gastric carcinomas.
- To analyze the frequency of alterations in ERBB, ERBB2, HST1, INT2, and LMYC genes during gastric cancer metastasis.
Main Methods:
- Southern blot hybridization was used to analyze DNA from primary and metastatic gastric tumors.
- The study examined 32 metastatic tumor samples from 12 autopsy cases and 89 primary gastric carcinomas.
Main Results:
- ERBB and ERBB2 gene amplification was observed in advanced primary gastric carcinomas.
- Amplification of the ERBB gene and allelic deletion of the LMYC gene were found in metastatic tumors.
- ERBB2 gene amplification was significantly more frequent in metastatic tumors compared to primary tumors, with some cases showing coamplification of HST1 and INT2.
Conclusions:
- Multi-alterations in oncogenes appear to occur during the progression and metastasis of human gastric carcinomas.
- Specific oncogene amplifications, particularly ERBB2, are associated with advanced and metastatic gastric cancer stages.