Analysis of CDKN2A, CDKN2B, CDKN2C, and cyclin Ds gene status in hepatoblastoma
Abstract
The status and the expression of cyclin-dependent kinase inhibitor A (CDKN2A) family genes, named CDKN2A, CDKN2B, and CDKN2C and of cyclin Ds (D1, D2, and D3) genes were investigated in 14 cases of human hepatoblastomas. These genes were selected because: 1) CDKN2A and CDKN2B are very frequently inactivated in human cancers; 2) cyclin Ds are overexpressed in several tumors and 3) CDKN2A is posttranscriptionally silenced in hepatocellular carcinomas. Structural analysis of the CDKN2A, CDKN2B, and CDKN2C genes in hepatoblastoma cases showed the absence of deletions and/or point mutations. Moreover, a detailed investigation of loss of heterozygosity at 9p21 and 1p32 (the chromosomal regions where CDKN2A genes are located) rules out the possible loss of one allele. Messenger RNA (mRNA) analysis showed that CDKN2C is expressed in all hepatoblastoma samples studied, while both CDKN2A and CDKN2B genes are not transcribed in the cancer specimens as well as in the matched normal liver tissues. Interestingly, an alternative mRNA expressed by the CDKN2A gene (beta-transcript) is detectable in 100% of the samples investigated. The analysis of cyclin D genes expression revealed that cyclin D1 is highly transcribed in normal hepatic tissue w...Continue Reading
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