Chromosomal instability and human hepatocarcinogenesis

Recently, many studies have identified losses and gains of several chromosomal loci in human hepatocellular carcinoma (HCC) with fine microsatellite analysis and comparative genomic hybridization. Although distribution of aberrant chromosomal arms differs among HCCs, loss of 1p, 4q, 6q, 8p, 9p, 10q, 13q, 16q and 17p, and gain of 1q, 6p, 8q, 17q and 20q have been recurrently reported, and loss of 4q and 16q seems to occur preferentially in hepatitis B virus-related HCCs. Accumulation of these aberrant chromosomal regions is associated with tumor progression, and some chromosomal aberrations, such as loss of 1p, are frequently identified in well-differentiated HCCs and also detected even in dysplastic nodule and cirrhotic nodule. This evidence suggests that chromosomal instability (CIN) emerges at an early stage during hepatocarcinogenesis and is successively inherent to tumor cells, resulting in acquisition of malignant phenotype. The molecular basis of CIN is beginning to be explored; however, several mechanisms may be involved for CIN of HCC.