The abnormalities of chromosome 8 in two hepatocellular carcinoma cell clones with the same genetic background and different metastatic potential.
OBJECTIVE
Two hepatocellular carcinoma (HCC) cell clones named MHCC97-H and MHCC97-L with different metastatic potential have recently been established from the same parent cell line MHCC97 in our institute. The cytogenetic alterations of these two clones were investigated in this study to explore the possible clues to the mechanism involved in HCC metastasis.


METHODS
Their chromosomal aberrations were analyzed with comparative genomic hybridization (CGH), chromosome-specific painting, and two-color fluorescence in situ hybridization (FISH).


RESULTS
The aberrations were found in a total of 17 chromosomes, and six kinds of the aberrations including gains of 1q, 7q, 8q, 20, and the losses of 8p23, 21q were found both in the two cell clones and their parent cell line MHCC97. Using modified CGH, with the DNA of MHCC97-L as control to test the MHCC97-H clone, the loss of 8p23 and the gain of 1q31-32, 8q21.3-22, 13q22, 17q22 were highlighted, and the most significant finding was on chromosome 8. Dual color FISH combining a pericentromeric probe and a BAC probe mapping at 8q23.1 was then performed to verify this result, and the signal ratios of the BAC to centromere were 1.43 in MHCC97-H and 1.45 in MHCC97-L, confirming the over-representations at 8q in both cells. Another interesting finding in the dual-color metaphase FISH was the intrachromosomal translocation of 8q to 8p (looked like an isochromosome 8) and non-reciprocal translocation of part of 8q to 4q, which was further clarified and proved by the FISH with whole chromosome 8 painting probe.


CONCLUSIONS
The high copies amplification on 8q, the formation of isochromosome 8, non-reciprocal translocation of partial 8q to 4q, and loss of 8p occurred at the same time and are the characteristic chromosomal aberrations of the two cell clones. The chromosome 8p, especially 8p23, might harbor some novel genes related to the HCC metastasis.
Yang
Jiong
J
Liver Cancer Institute & Zhongshan Hospital of Fudan University, 136 Yi Xue Yuan Road, 200032, Shanghai, China.
Qin
Lun-Xiu
LX
Ye
Sheng-Long
SL
Liu
Yin-Kun
YK
Li
Yan
Y
Gao
Dong-Mei
DM
Chen
Jie
J
Tang
Zhao-You
ZY
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000556:secondary; D002869:Chromosome Aberrations; D020223:Chromosome Painting / Q000379:methods; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003001:Cloning, Molecular; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization / Q000379:methods; D014407:Tumor Cells, Cultured