A comprehensive karyotypic study on human hepatocellular carcinoma by spectral karyotyping

The current paucity of cytogenetic information on hepatocellular carcinoma (HCC) reflects the difficulties in culturing hepatocytes in vitro. Here, we report on the successful culture of 15 HCC cases. Chromosome aneuploidy ra nging from a near-diploid to hyperhexaploid karyotype was found, but their complete karyotypic interpretations were hampered by the presence of many u nidentifiable rearrangements. Spectral karyotyping (SKY) was used to elucid ate structural changes in these HCC samples and 3 liver cancer cell lines ( PLC/PRF/5, Hep3B, and HepG2). Frequent structural abnormalities were found on chromosomes 1 (13 of 15 cases;3 of 3 cell lines), 8 (10 of 15 cases; 2 o f 3 cell lines), 17 (9 of 15 cases; 3 of 3 cell lines), and 19 (9 of 15 cas es; 1 of 3 cell lines). In particular, the chromosome regions 1p13-q21, 8p1 2-q21, 17p11-q12, 17q22, and 19p10-q13.1 were involved in multiple rearrang ements. SKY analysis also suggested several previously undescribed breakpoi nts in HCC. These breakpoints, predominantly pericentromeric, clustered aro und the chromosome bands 2q33-q34, 3p13-q12, 4p14-q12, 5p10-q11, 7p12-q11, 10q10-q11, 11q10, 11q113-q21,12q10-q13,12q22-q23,13q10-q14,15q10, 18p11-q11 , 20p11-q13.1, 21q10, and 22q10. When tumor sizes were compared, a signific antly higher number of structural abnormalities was found in tumors larger than 4 cm (P = .007). Rearrangements such as t(1;8), t(1;11), t(1;19), and t(17;21) that were identified in both primary tumors and cell lines might r epresent markers that reflect proliferative advantages. Although SKY analys is did not indicate consistent translocations, it suggested nonrandom break points, predominantly in the pericentromeric region, on a number of chromos omes. These breakpoint clusters may thus prove to be more important in the liver carcinogenesis and targets for further molecular investigations.