Investigation in liver tissues and cell lines of the transcription of 13 genes mapping to the 16q24 region that are frequently deleted in hepatocellular carcinoma.
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.
Riou
Philippe
P
Service de Biochimie et Biologie moléculaire and Centre Hépatobiliaire Hôpital Universitaire Paul Brousse, UPRES 1596-Faculté de Médecine Paris-Sud, 94804 Villejuif Cedex, France.
Saffroy
Raphaël
R
Comoy
Jérome
J
Gross-Goupil
Marine
M
Thiéry
Jean-Paul
JP
Emile
Jean-François
JF
Azoulay
Daniel
D
Piatier-Tonneau
Dominique
D
Lemoine
Antoinette
A
Debuire
Brigitte
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019656:Loss of Heterozygosity / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger