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Expression mapping at 12p12-13 in advanced prostate carcinoma
Adam S Kibel1, John Huagen, Chan Guo
1Department of Surgery, Division of Urology, Washington University School of Medicine, 4960 Children's Place, St. Louis, MO 63110, USA. kibela@msnotes.wustl.edu
International Journal of Cancer
|March 5, 2004
Summary
Researchers identified key genes, DUSP16, FLJ10298, and BCLG, downregulated in prostate cancer. These genes, located in a deleted region of chromosome 12p, may be crucial tumor suppressors involved in prostate carcinoma initiation and progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- A putative prostate cancer tumor-suppressor gene was previously mapped to chromosome 12p12-13.
- Initial attempts to identify the gene using mutational and methylation analyses were unsuccessful.
Purpose of the Study:
- To narrow the candidate region for a prostate cancer tumor-suppressor gene using deletion mapping.
- To identify candidate tumor-suppressor genes within the minimal deleted region through expression analysis.
Main Methods:
- Loss of heterozygosity analysis was performed on 99 tumor and normal DNA pairs using polymorphic markers.
- Quantitative reverse transcription PCR (RT-PCR) was used to determine the expression levels of 10 candidate genes in various prostate cancer samples and cell lines.
Main Results:
- A minimal deletion region of approximately 500 kb was identified on chromosome 12p, bounded by D12S391 and A002Q26.
- Three genes (DUSP16, FLJ10298, and BCLG) were found to be significantly downregulated in both clinical prostate tumors and prostate cancer cell lines.
- These downregulated genes are located within or near the minimal deleted region.
Conclusions:
- DUSP16, FLJ10298, and BCLG are potential prostate cancer tumor suppressors.
- The downregulation of these genes suggests their critical role in the initiation or progression of prostate carcinoma.