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Tumor suppressor genes involved in metastasis of lung and colorectal carcinomas
J Yokota1, K Ookawa, R Nishikawa
1Section of Studies on Metastasis, National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
Inactivation of tumor suppressor genes is now believed to play an important role in various progression stages of human cancers. To clarify the possible involvement of tumor suppressor gene inactivation in the acquisition of metastatic potential in lung and colorectal carcinoma cells, we examined various genetic alterations in both primary tumors and metastases obtained from patients with lung and colorectal carcinomas. In lung carcinoma, loss of heterozygosity on chromosomes 3p, 13q, and 17p is a common genetic alteration, and both RB and p53 genes are inactivated as a result of chromosome 13q and 17p losses. In some cases, allelic loss on chromosome 11p and amplification of myc family oncogenes occur during tumor progression. In colorectal carcinoma, p53 and DCC alterations were detected in 100% of metastases, and sequential accumulation of allelic losses on chromosomes 13q, 14q, and 18q in the process of metastasis was observed. These results indicate that a subset of tumor suppressor genes is involved in metastasis of lung and colorectal carcinomas.
Insights
Tumor suppressor gene inactivation is crucial in cancer progression. This study reveals specific genetic alterations linked to metastasis in lung and colorectal cancers, identifying key genes involved in tumor spread.
Area of Science:
- Oncology
- Cancer Genetics
- Molecular Biology
Background:
- Tumor suppressor gene inactivation is implicated in cancer progression.
- Understanding genetic alterations in metastasis is vital for effective cancer treatment.
Purpose of the Study:
- To investigate the role of tumor suppressor gene inactivation in the metastatic potential of lung and colorectal carcinoma cells.
- To identify specific genetic alterations associated with metastasis in these cancer types.
Main Methods:
- Analysis of genetic alterations in primary tumors and metastases from lung and colorectal carcinoma patients.
- Examination of gene losses and amplifications, including specific chromosomal regions and oncogenes.
Main Results:
- Lung carcinoma: Common alterations include loss of heterozygosity on chromosomes 3p, 13q, and 17p, with RB and p53 gene inactivation. Myc family oncogene amplification was also observed.
- Colorectal carcinoma: p53 and DCC alterations were present in all metastases. Sequential allelic losses on chromosomes 13q, 14q, and 18q occurred during metastasis.
Conclusions:
- A subset of tumor suppressor genes plays a significant role in the metastasis of lung and colorectal carcinomas.
- Specific genetic alterations identified are potential biomarkers for cancer metastasis and therapeutic targets.