Related Experiment Videos
Absence of ST7 gene alterations in human cancer
Seung Myung Dong1, David Sidransky
1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Abstract:
The ST7 gene was cloned and mapped to chromosome 7q31.1-q31.2, a region suspected of containing a tumor suppressor gene involved in a variety of human cancers. Subsequent investigation described the presence of ST7 mutations in human cell lines derived from breast tumors and primary colon carcinoma. Introduction of the ST7 cDNA into a prostate cancer-derived cell line abrogated in vivo tumorigenecity in nude mice. To clarify the role of the ST7 gene in cancer, we scrutinized primary head and neck squamous cell carcinomas, invasive ductal carcinomas of the breast, and adenocarcinomas of the colon. Loss of heterozygosity of D7S522/D7S677 was detected in 24% (4 of 17) of head and neck squamous cell carcinomas, 17% (2 of 12) of invasive ductal carcinomas of the breast, and 33% (8 of 24) of adenocarcinomas of the colon, but no somatic mutations were found in any of these specimens. We then searched for mutations in breast cancer cell lines and found a complete wild-type sequence in all, including cell lines previously reported to harbor mutations. We believe that the ST7 gene is not a primary target of inactivation in most human cancers with loss of heterozygosity at 7q31.1-q31.2.
Insights
The ST7 gene, suspected as a tumor suppressor, showed no mutations in common human cancers. This suggests ST7 is not a primary target for inactivation in these cancers.
Area of Science:
- Oncology
- Cancer Genetics
Background:
- The ST7 gene, located on chromosome 7q31.1-q31.2, was hypothesized to be a tumor suppressor gene implicated in various human cancers.
- Previous studies indicated ST7 mutations in breast and colon cancer cell lines, and its introduction into a prostate cancer cell line reduced tumor formation.
Purpose of the Study:
- To investigate the role of the ST7 gene in the development of human cancers.
- To determine if ST7 gene mutations or loss of heterozygosity (LOH) are prevalent in head and neck, breast, and colon cancers.
Main Methods:
- Analysis of primary head and neck squamous cell carcinomas, invasive ductal carcinomas of the breast, and adenocarcinomas of the colon.
- Detection of loss of heterozygosity (LOH) at D7S522/D7S677 markers.
- Somatic mutation screening of the ST7 gene in primary tumors and breast cancer cell lines.
Main Results:
- Loss of heterozygosity (LOH) at 7q31.1-q31.2 was observed in 24% of head and neck cancers, 17% of breast cancers, and 33% of colon cancers.
- No somatic mutations in the ST7 gene were detected in any of the analyzed primary tumor specimens.
- Screening of breast cancer cell lines revealed a complete wild-type ST7 sequence, contradicting previous reports.
Conclusions:
- The ST7 gene is unlikely to be a primary target for inactivation in the majority of human cancers exhibiting LOH at chromosome 7q31.1-q31.2.
- The observed LOH may be due to inactivation of other tumor suppressor genes in the 7q31.1-q31.2 region.
- Further research is needed to fully elucidate the function of ST7 in cancer biology.