High resolution analysis of cytogenetic aberrations in hepatocellular carcinoma using oligo array CGH. A. De Witte1, L. Guo2, J. Collins1, Y. Dragan2. 1) Agilent Technologies, Inc., Santa Clara, CA; 2) National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR.
Hepatocellular carcinoma (HCC) is one of the most commonly occurring tumors in the world. The major etiologies of HCC are chronic hepatitis B virus (HBV) or hepatitis C (HCV) infection, exposure to aflatoxins, chronic liver disease and alcohol abuse. Chromosomal aberrations play an important role in liver cancer development and progression. In this study, we report the analysis of genomic changes in DNA samples collected from 11 HCC patients (aged 46-72; 10 male) comparing the neoplasms with the surrounding tissue from the same individual. Microarrays consisting of ~185,000 in situ synthesized 60-mer oligonucleotide probes optimized for array CGH (Comparative Genomic Hybridization) applications (Agilent Technologies) were used. We compare our results with published aberrations identified by lower resolution techniques such as conventional CGH based on the use of fluorescence in situ hybridization (FISH), spectral karyotyping (SKY) and BAC (bacterial artificial chromosomes) array-based CGH. We observed recurrent DNA copy number changes, including a characteristic 8p deletion and 8q amplification. We mapped several breakpoint regions associated with aberrations to the gene resolution level and we discovered novel small aberrations in several samples. Our results contribute to a more detailed description of genetic aberrations associated with HCC and demonstrate that oligo array CGH enables the mapping of breakpoints at a much higher resolution than traditional techniques.