Abstract
Purpose
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.
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References
Aalto Y, Eriksson L, Seregard S, Larsson O, Knuutila S (2001) Concomitant loss of chromosome 3 and whole arm losses and gains of chromosome 1, 6, or 8 in metastasizing primary uveal melanoma. Invest Ophthalmol Vis Sci 42:313–317
Chan KL, Lee JM, Guan XY, Fan ST, Ng IO (2002) High-density allelotyping of chromosome 8p in hepatocellular carcinoma and clinicopathologic correlation. Cancer 94:3179–3185
Chang J, Kim NG, Piao Z, Park C, Park KS, Paik YK, Lee WJ, Kim BR, Kim H (2002) Assessment of chromosomal losses and gains in hepatocellular carcinoma. Cancer Lett 182:193–202
Chu LW, Pettaway CA, Liang JC (2001) Genetic abnormalities specifically associated with varying metastatic potential of prostate cancer cell lines as detected by comparative genomic hybridization. Cancer Genet Cytogenet 127:161–167
Dierlamm J, Rosenberg C, Stul M, Pittaluga S, Wlodarska I, Michaux L, Dehaen M, Verhoef G, Thomas J, Zeller W, Bakker-Schut T,Cassiman JJ, Raap A, De Wolf-Peeters C, Van den Berghe H, Hagemeijer A (1997) Characteristic pattern of chromosomal gains and losses in marginal zone B-cell lymphoma detected by comparative genomic hybridization. Leukemia 11:747–758
Dierlamm J, Stefanova M, Wlodarska I, Michaux L, Hinz K, Penas EM, Maes B, Hagemeijer A, De Wolf-Peeters C, Hossfeld DK (2001) Chromosomal gains and losses are uncommon in hairy cell leukemia: a study based on comparative genomic hybridization and interphase fluorescence in situ hybridization. Cancer Genet Cytogenet 128:164–167
Ishii H, Vecchione A, Murakumo Y, Baldassarre G, Numata S, Trapasso F, Alder H, Baffa R, Croce CM (2001) FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis. Proc Natl Acad Sci USA 98:10374–10379
Kallioniemi O-P, Kallioniemi A, Piper J, Isola J, Waldman FM, Gray JW, Pinkel D (1994) Optimizing comparative genomic hybridization for the analysis of DNA sequence copy number changes in solid tumours. Genes Chromosomes Cancer 10:231–243
Kusano N, Shiraishi K, Kubo K, Oga A, Okita K, Sasaki K (1999) Genetic aberrations detected by comparative genomic hybridization in hepatocellular carcinomas: their relationship to clinicopathological features. Hepatology 29:1858–1862
Li Y, Tang ZY, Ye SL, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH (2001) Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol 7:630–636
Liao C, Zhao M, Song H, Uchida K, Yokoyama KK, Li T (2000) Identification of the gene for a novel liver-related putative tumor suppressor at a high-frequency loss of heterozygosity region of chromosome 8p23 in human hepatocellular carcinoma. Hepatology 32: 721–727
Mehra S, Messner H, Minden M, Chaganti RS (2002) Molecular cytogenetic characterization of non-Hodgkin lymphoma cell lines. Genes Chromosomes Cancer 33:225–234
Nishizaki T, DeVries S, Chew K, Goodson WH 3rd, Ljung BM, Thor A, Waldman FM (1997) Genetic alterations in primary breast cancers and their metastases: direct comparison using modified comparative genomic hybridization. Genes Chromosomes Cancer 19:267–272
Pisani P, Parkin M, Bray F, Ferlay J (1999) Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83:18–29
Qin LX, Tang ZY, Sham JS, Ma ZC, Ye SL, Zhou XD, Wu ZQ, Trent JM, Guan XY (1999) The association of chromosome 8p deletion and tumor metastasis in human hepatocellular carcinoma. Cancer Res 59:5662–5665
Qin LX, Tang ZY, Ye SL, Liu YK, Ma ZC, Zhou XD, Wu ZQ, Lin ZY, Sun FX, Tian J, Guan XY, Pack SD, Zhuang ZP (2001) Chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma when high and low metastatic models are compared. J Cancer Res Clin Oncol 127:482–488
Rao UN, Gollin SM, Beaves S, Cieply K, Nalesnik M, Michalopoulos GK (2001) Comparative genomic hybridization of hepatocellular carcinoma: correlation with fluorescence in situ hybridization in paraffin-embedded tissue. Mol Diagn 6:27–37
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratorymanual, 2nd edn. Cold Spring Harbor Laboratory, New York
Steiner T, Junker K, Burkhardt F, Braunsdorf A, Janitzky V, Schubert J (2002) Gain in chromosome 8q correlates with early progression in hormonal treated prostate cancer. Eur Urol 41:167–171
Sun FX, Tang ZY, Lui KD, Ye SL, Xue Q, Gao DM, Ma ZC (1996) Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer 66:239–243
Tabor MP, van Houten VM, Kummer JA, Vosjan MJ, Vlasblom R, Snow GB, Leemans CR, Braakhuis BJ, Brakenhoff RH (2002) Discordance of genetic alterations between primary head and neck tumors and corresponding metastases associated with mutational status of the TP53 gene. Genes Chromosomes Cancer 33:168–177
Tang ZY (2001) Hepatocellular carcinoma: cause, treatment and metastasis. World J Gastroenterol 7:445–454
Thor AD, Eng C, Devries S, Paterakos M, Watkin WG, Edgerton S, Moore DH 2nd, Etzell J, Waldman FM (2002) Invasive micropapillary carcinoma of the breast is associated with chromosome 8 abnormalities detected by comparative genomic hybridization. Hum Pathol 33:628–631
Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, Xue Q (1999) New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expression of the factors associated with metastasis. Br J Cancer 81:814–821
Virgin JB, Hurley PM, Nahhas FA, Bebchuk KG, Mohamed AN, Sakr WA, Bright RK, Cher ML (1999) Isochromosome 8q formation is associated with 8p loss of heterozygosity in a prostate cancer cell line. Prostate 41:49–57
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532
Wilkens L, Bredt M, Flemming P, Kubicka S, Klempnauer J, Kreipe H (2000) Cytogenetic aberrations in primary and recurrent fibrolamellar hepatocellular carcinoma detected by comparative genomic hybridization. Am J Clin Pathol 114:867–874
Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC (1998) Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer Res 58:2196–2199
Zhang LH, Qin LX, Ma ZC, Ye QH, Wu X, Huang W, Tang ZY et al (2003) Allelic imbalance regions on chromosomes 8p, 17p and 19p related to metastasis of hepatocellular carcinoma: comparison between matched primary and metastatic lesions in 22 patients by genome-wide microsatellite analysis. J Cancer Res Clin Oncol (in press)
Zhou XD, Tang ZY, Yu YQ, Yang BH, Lu JZ, Lin ZY, Ma ZC, Zhang BH (1994) Recurrence after resection of alpha fetoprotein positive hepatocellular carcinoma. J Cancer Res Clin Oncol 120:369–373
Zondervan PE, Wink J, Alers JC, IJzermans JN, Schalm SW, de Man RA, van Dekken H (2000) Molecular cytogenetic evaluation of virus-associated and non-viral hepatocellular carcinoma: analysis of 26 carcinomas and 12 concurrent dysplasias. J Pathol 192:207–215
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Supported by China National Key Basic Research Program (The 973 Project) Grant G1998051200, and the National Scientific Funding for Younger Scientists (C3000075), the Key Project from the Ministry of Education of China, and the Key Med-X Project of Fudan University.
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Yang, J., Qin, LX., Ye, SL. et al. The abnormalities of chromosome 8 in two hepatocellular carcinoma cell clones with the same genetic background and different metastatic potential. J Cancer Res Clin Oncol 129, 303–308 (2003). https://doi.org/10.1007/s00432-003-0436-8
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DOI: https://doi.org/10.1007/s00432-003-0436-8