Analysis of the mechanisms mediating tumor-specific changes in gene expression in human liver tumors
The availability of genomic resources makes possible the study of liver cancer by innovative approaches allowing an efficient characterization of the differences between tumor and normal samples. This study presents an effective, combinatorial methodology for genome-scale characterization of tumors. First, changes in gene expression, as monitored on RNA expression arrays, were identified as the HCC transcriptome. Then, I optimized a new method of chromatin immunoprecipitation (ChIP) experiments to permit the analysis of liver biopsies and cell populations in numbers as low as 10,000 cells. Using the modified ChIP protocol, I characterized the chromatin modifications and defined active and inactive gene promoters on a genome-wide scale. Next, I employed a novel method named “virtual comparative genomic hybridization” (vCGH) to study copy number changes. Finally, through comparison of RNA Polymerase II binding, chromatin structure, and copy number changes, I determined that the major contributor to the creation of the liver tumor transcriptome was changes in gene copy number.
0379: Cellular biology