Clonal diversity and its imphcution in multistage development of hepatocellnlar caronoma

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Genomic diversity and its implication in multistage development were explored by analyzing chrmosomal alterations found in multiple liver nodule obtained from patients with hepatocellular carcinoma who had and one living donor orthotopic liver transplantation.Tumor and non tumor tissue were obtained at the time of surgery, from patients who had provided written informed consent DNA was extracted by using conventional proteinase K/phenol-chloroform method Four-hundred pane of PCR primers that distribute almost equally throughout 22 autosome and X chromosome wee used to amplify microsatellite loci. Allelic imbalances were determined on the bass of the area under the curve of PCR product that derived from the tumor and the non-tumor sample Single nucleotide polymorphism (SNP) array were used to discriminate chromosomal and losses.Seventy-two patients with hepatocellular carcinoma had received living-donor liver transplantation in between April 2004 and August and August 2007. A total of 20 nodules were obtained from eight of these patients. Recurrent chromosome alterations, such as -1p, +1q, +5, +7, -8p, +8q, -16q, -17p, were detected. Chromosomal relationship analysis revealed that seven patients out of eight had metastatic nodule, while only one patient had tumors of multicentric origin.Furthermore, chromosome analysis of 30 nodules m a patient detected both genetically stable tumors that was hind to have common chromosome alterations such as -1p, +1q, -6q, -16q, +22q, and unstable tumors that had multiple alterations throughout almost all chromosome.Although chromosomal alterations detected m hepatocellular carcinoma m patients with end-stage liver disease were generally stable, chromosomal instability might occur by an unknown but possibly different mechanism.