STRUCTURE AND EXPRESSION OF THE CYCLIN-A GENE IN HUMAN PRIMARY LIVER-CANCER - CORRELATION WITH FLOW CYTOMETRIC PARAMETERS

Background/Aims: The cyclin A gene plays an important role in both the S and G2-M phases of the cell cycle, and has been identified at a site of hepatitis B virus DNA integration in a human liver cancer. We analyzed tumorous and non-tumorous samples from patients with primary liver cancer to determine whether a) the cyclin A gene is rearranged in liver tumors and b) the cyclin A transcript level correlates with the percentage of proliferating cells. Methods: Samples from 43 patients were analyzed by Southern blot, Cyclin A RNA accumulation was evaluated in 18 cases by slot blot and correlated with the percentage of cells in S plus G2-M phases defined by bow cytometry. Results: No rearrangement of the cyclin A gene was found in tumorous compared to non-tumorous tissue. A very strong positive correlation was found between the cyclin A RNA level and the cumulative percentage of cells in S plus G2-M phases (r=0,99; p<0,0001). Conclusions: This in vivo study shows that the expression of cyclin A RNA correlates with the percentage of proliferating cells in primary liver cancer. Thus, cyclin A is a new potential liver tumor cell proliferation index. (C) Journal of Hepatology.