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Molecular Oncology, Markers, Clinical Correlates |
Service de Biochimie et Biologie moléculaire [P. R., R. S., J. C., M. G-G., J-P. T., A. L., B. D.], Service dAnatomie pathologique [J-F.E.], and Centre Hépatobiliaire Hôpital Universitaire Paul Brousse [D. A.], UPRES 1596-Faculté de Médecine Paris-Sud, 94804 Villejuif Cedex, France, and Génétique Moléculaire et Biologie du Développement, FRE 2376, Centre National de la Recherche Scientifique, 94801 Villejuif Cedex, France [D. P-T.]
Many studies have associated chromosomal deletions in the 16q24 region with human cancers, including hepatocellular carcinoma. A more limited region around the microsatellite D16S402 has been shown implicated in the metastatic spread of hepatocellular carcinoma, prostate cancer, and Wilms tumors. It is likely that one or more tumor suppressor genes are located in this 16q24 area.
We used SYBR Green reagents to quantify, by real-time quantitative RT-PCR, the production of mRNA for 13 genes mapping to 16q24. The locations of these genes were determined from published human genome sequencing data. We studied mRNA levels in 10 liver tumor tissues, 10 nontumor liver tissues, five hepatoma cell lines, and in isolated hepatocytes. Results were compared with those for loss of heterozygosity observed in the D16S402 region and recurrence.
No down-regulation was observed in tumor tissues. Two genes were consistently overexpressed: OKL38 and CDH13. CDH13, which functions in cell-cell adhesion, seems to be involved in liver carcinogenesis. However, no relationship was observed between the expression of this gene and changes in the D16S402 microsatellite or tumor recurrence. None of the other genes tested seemed to be a good candidate for a major tumor suppressor gene in liver carcinogenesis.
Our results suggest that additional unknown genes involved in carcinogenesis are located in the 16q24 area.
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