尋找位於人類第十六號染色體上可能與肝癌發生有關抑癌基因的研究

Hepatocellular carcinoma (HCC) is one of the most common cancer in the world and is
the leading cause of cancer death in Taiwan. The prognosis of this cancer is extremely poor with
survival of only several months after symptoms occurred. Elucidation of the basic genetic
changes of HCC is important for the understanding and treatment of this cancer. Cancer is
usually accompanied with genetic alternations either through the activation of cellular oncogene
or the inactivation of cancer suppressor gene. The recently identified short tandem repeat, the
microsatellite, which is widely distributed throughout the whole human genome. Identification
of disease genes as well as tumor suppressor genes by microsatellite polymorphism. have been
published recently. In this study we use microsatellite marker to analyze 88 cases of HCCs, most
of them are small in size, in order to study the genetic changes of HCC and to further narrow
down the common LOH sites in 16q.
In this study, we have used 35 microsatellite markers for further fine mapping of LOH.
We have confirmed the most frequent regions of LOH for HCC are 16q12.1, 16q22, and 16q24.
After analyzing these information, we started to screen the human BAC(Bacterial Artificial
chromosome)library by these markers at 16q12.1 and we identified 15 clones. Exon trapping
system is used to search the putative exon sequences of BAC genomic clones. Two exon-like
sequences are identical to the KIAA1005 gene. Homozygous deletion of KIAA1005 was found
in 37%(10 /27) HCCs. These data suggested that the KIAA1005 might be the putative tumor
suppressor genes at chromosome 16q12.1.
The function of KIAA is unknown. From the predicted sequences, we can predict that the gene might be a transcription factor or be correlated with phosphorylation. Furthermore, it
seems have different splicing form and play different role in HCC development. However, this
need further investigation to elucidate KIAA function.