Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by restriction landmark genomic scanning

Background/Aims: One of the unique features of advanced hepatocellular carc inoma (HCC) is the morphological heterogeneity in a single tumor nodule, In order to investigate the intratumoral genomic heterogeneity of HCC, we per formed Restriction Landmark Genomic Scanning (RLGS), which allows genomic D NAs to be surveyed at approximately 2000 landmark sites in a single 2-dimen sional gel electrophoresis. Methods: RLGS profiles of two regions from a single HCC nodule in six patie nts were compared with nontumorous liver tissue. Four HCCs consisting of mo derately-differentiated cells were separated into several small parts by th in fibrous septa, but not encapsulated. DNA samples were obtained from both parts of these so-called "nodule-in-nodule" HCC. Two HCCs consisting of we ll-differentiated cells which did not have a definite partition appeared pa thologically homogeneous, and two independent regions of the HCC were used for the analysis. Results: All six HCCs demonstrated different RLGS profiles (in total about 160 different spots) from the corresponding non-tumorous liver, and the num ber of different spots was greater id the 4 moderately-differentiated nodul e-in-nodule HCCs (39-68 spots) than in the 2 web-differentiated homogeneous HCCs (6 and 3 spots). RLGS profiles of the two parts were different to eac h other in all 4 nodule-in-nodule HCCs. On the other hand, two other homoge neous HCCs showed the same RLGS profiles in the two regions. Conclusion: Thus, intratumoral genomic heterogeneity was demonstrated in th e advanced HCC samples, and the genomic alterations may relate to the progr ession of HCC.