Abstract
Hepatoblastoma is a malignant paediatric liver tumour. In order to approach the genetic background of this malignancy we have screened a panel of eighteen cases from Europe and Japan for chromosomal imbalances using comparative genomic hybridization (CGH). The most frequent losses included chromosomal regions 13q21–q22 (28%) and 9p22-pter (22%), while the most frequent gains occurred on 2q23–q24 (33%), 20q (28%) and 1q24–q25 (28%). A significant difference in CGH alterations between the tumours from patients of Caucasian and Japanese was revealed where loss of 13q was found only in the Japanese samples. In conclusion, the findings indicate several candidate regions for suppressor genes and oncogenes potentially involved in the hepatoblastomas of different ethnic origin. © 2000 Cancer Research Campaign
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References
Ahn HJ, Kwon KW, Choi YJ, Kim HJ, Hong SP, Oh D and Chung JS (1997) Mixed hepatoblastoma in an adult – a case report and literature review. Journal of Korean Medical Science 12: 369–373
Albrecht S, von Schweinitz D, Waha A, Kraus JA, von Deimling A and Pietsch T (1994) Loss of maternal alleles on chromosome arm 11p in hepatoblastoma. Cancer Research 54: 5041–5044
Ammann RA, Plaschkes J and Leibundgut K (1999) Congenital hepatoblastoma: a distinct entity?. Medical and Pediatric Oncology 32: 466–468
Anneren G, Nordlinder H and Hedborg F (1992) Chromosome aberrations in an alpha-fetoprotein-producing hepatoblastoma. Genes, Chromosomes and Cancer 4: 99–100
Balogh E, Swanton S, Kiss C, Jakab ZS, Secker-Walker LM and Oláh É (1998) Fluorescence in situ hybridization reveals trisomy 2q by insertion into 9p in hepatoblastoma. Cancer Genetics and Cytogenetics 102: 148–150
Bove KE, Soukup S, Ballard ET and Ryckman F (1996) Hepatoblastoma in a child with trisomy 18: cytogenetics, liver anomalies, and literature review. Pediatric Pathology and Laboratory Medicine 16: 253–262
Chen WT (1996) Proteases associated with invadopodia, and their role in degradation of extracellular matrix. Enzyme and Protein 49: 59–71
Doss BJ, Vicari J, Jacques SM and Qureshi F (1998) Placental involvement in congenital hepatoblastoma. Pediatric and Developmental Pathology 1: 538–542
Douglass EC, Green AA, Hayes FA, Etcubanas E, Horowitz M and Wilimas JA (1985) Chromosome 1 abnormalities: a common feature of pediatric solid tumors. Journal of the National Cancer Institute 75: 51–54
Fletcher JA, Kozakewich HP, Pavelka K, Grier HE, Shamberger RC, Korf B and Morton CC (1991) Consistent cytogenetic aberrations in hepatoblastoma: a common pathway of genetic alterations in embryonal liver and skeletal muscle malignancies?. Genes, Chromosomes and Cancer 3: 37–43
Gray SG, Eriksson T, Ekström C, von Schweinitz D, Kogner P, Sandstedt B, Pietsch T and Ekström TJ (2000) Altered expression of members of the IGF-axis in hepatoblastomas. British Journal of Cancer 82, (9)1561–1567
Hu J, Wills M, Baker BA and Perlman EJ (2000) Comparative genomic hybridization analysis of hepatoblastomas. Genes, Chromosomes and Cancer 27: 196–201
Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F and Pinkel D (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258: 818–821
Knuutila S, Aalto Y, Autio K, Bjorkqvist AM, El-Rifai W, Hemmer S, Huhta T, Kettunen E, Kiuru-Kuhlefelt S, Larramendy ML, Lushnikova T, Monni O, Pere H, Tapper J, Tarkkanen M, Varis A, Wasenius VM, Wolf M and Zhu Y (1999) DNA copy number losses in human neoplasms. American Journal of Pathology 155: 683–694
Kraus JA, Albrecht S, Wiestler OD, von Schweinitz D and Pietsch T (1996) Loss of heterozygosity on chromosome 1 in human hepatoblastoma. International Journal of Cancer 67: 467–471
Kuniyasu H, Yasui W, Shimamoto F, Fujii K, Nakahara M, Asahara T, Dohi K and Tahara E (1996) Hepatoblastoma in an adult associated with c-met proto-oncogene imbalance. Pathology International 46: 1005–1010
Larramendy ML, El-Rafai W and Knuutila S (1998) Comparison of fluorescein isothiocyanate- and Texas red-conjugated nucleotides for direct labeling in Comparative Genomic Hybridization. Cytometry 31: 174–179
Lin YW, Sheu JC, Huang GT, Lee HS, Chen CH, Wang JT, Lee PH and Lu FJ (1999) Chromosomal abnormality in hepatocellular carcinoma by comparative genomic hybridisation in Taiwan. European Journal of Cancer 35: 652–658
Mares J, Polanska V, Gorgens H, Sedlacek Z, Marikova T, Bocek P, Kodet R, Schackert J and Goetz P (1998) Oncogene amplification and expression in pediatric solid tumors. Neoplasma 45: 123–127
Mascarello JT, Jones MC, Kadota RP and Krous HF (1990) Hepatoblastoma characterized by trisomy 20 and double minutes. Cancer Genetics and Cytogenetics 47: 243–247
Mathew S, Scanlan MJ, Mohan Raj BK, Murty VV, Garin-Chesa P, Old LJ, Rettig WJ and Chaganti RS (1995) The gene for fibroblast activation protein alpha (FAP), a putative cell surface-bound serine protease expressed in cancer stroma and wound healing, maps to chromosome band 2q23. Genomics 25: 335–337
Montagna M, Menin C, Chieco-Bianchi L and D’Andrea E (1994) Occasional loss of constitutive heterozygosity at 11p15.5 and imprinting relaxation of the IGF-II maternal allele in hepatoblastoma. Journal of Cancer Research and Clinical Oncology 120: 732–736
Morita K, Okabe I, Uchino J, Watanabe I, Iwabuchi M, Matsuyama S, Takahashi H, Nakajo T, Hirai Y, Tsuchida Y, Katsumata K, Hasegawa H, Nishi T, Okamoto E and Ikeda K (1983) The proposed Japanese TNM classification of primary liver carcinoma in infants and children. Japanese Journal of Clinical Oncology 13: 361–369
Nagai H, Pineau P, Tiollais P, Buendia MA and Dejean A (1997) Comprehensive allelotyping of human hepatocellular carcinoma. Oncogene 14: 2927–2933
Nagata T, Mugishima H, Shichino H, Suzuki T, Chin M, Koshinaga S, Inoue M and Harada K (1999) Karyotypic analyses of hepatoblastoma – report of two cases and review of the literature suggesting chromosomal loci responsible for the pathogenesis of this disease. Cancer Genetics and Cytogenetics 114: 42–50
Parada LA, Bardi G, Hallen M, Hagerstrand I, Tranberg KG, Mitelman F and Johansson B (1997) Cytogenetic abnormalities and clonal evolution in an adult hepatoblastoma. American Journal of Surgical Pathology 21: 1381–1386
Park JP, Ornvold KT, Brown AM and Mohandas TK (1999) Trisomy 2 and 19, and tetrasomy 1q and 14 in hepatoblastoma. Cancer Genetics and Cytogenetics 115: 86–87
Perilongo G and Shafford EA (1999) Liver tumours. European Journal of Cancer 35: 953–958
Rodriguez E, Reuter VE, Mies C, Bosl GJ and Chaganti RS (1991) Abnormalities of 2q: a common genetic link between rhabdomyosarcoma and hepatoblastoma?. Genes, Chromosomes and Cancer 3: 122–127
Sainati L, Leszl A, Stella M, Montaldi A, Perilongo G, Rugge M, Bolcato S, Iolascon A and Basso G (1998) Cytogenetic analysis of hepatoblastoma: hypothesis of cytogenetic evolution in such tumors and results of a multicentric study. Cancer Genetics and Cytogenetics 104: 39–44
Sakakura C, Hagiwara A, Taniguchi H, Yamaguchi T, Yamagishi H, Takahashi T, Koyama K, Nakamura Y, Abe T and Inazawa J (1999) Chromosomal aberrations in human hepatocellular carcinomas associated with hepatitis C virus infection detected by comparative genomic hybridization. British Journal of Cancer 80: 2034–2039
Scanlan MJ, Raj BK, Calvo B, Garin-Chesa P, Sanz-Moncasi MP, Healey JH, Old LJ and Rettig WJ (1994) Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proceedings of the National Academy of Sciences of the United States of America 91: 5657–5661
Schneider NR, Cooley LD, Finegold MJ, Douglass EC and Tomlinson GE (1997) The first recurring chromosome translocation in hepatoblastoma: der(4)t(1;4)(q12;q34). Genes, Chromosomes and Cancer 19: 291–294
Sheu JC, Lin YW, Chou HC, Huang GT, Lee HS, Lin YH, Huang SY, Chen CH, Wang JT, Lee PH, Lin JT, Lu FJ and Chen DS (1999) Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan. British Journal of Cancer 80: 468–476
Steenman M, Tomlinson G, Westerveld A and Mannens M (1999) Comparative genomic hybridization analysis of hepatoblastomas: additional evidence for a genetic link with Wilms tumor and rhabdomyosarcoma. Cytogenetics and Cell Genetics 86: 157–161
Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, Dahan K, Childs S, Ling V, Tanner MS, Kagalwalla AF, Nemeth A, Pawlowska J, Baker A, Mieli-Vergani G, Freimer NB, Gardiner RM and Thompson RJ (1998) A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nature Genetics 20: 233–238
Swarts S, Wisecarver J and Bridge JA (1996) Significance of extra copies of chromosome 20 and the long arm of chromosome 2 in hepatoblastoma. Cancer Genetics and Cytogenetics 91: 65–67
Teraguchi M, Nogi S, Ikemoto Y, Ogino H, Kohdera U, Sakaida N, Okamura A, Hamada Y and Kobayashi Y (1997) Multiple hepatoblastomas associated with trisomy 18 in a 3-year-old girl. Pediatric Hematology and Oncology 14: 463–467
Tonk VS, Wilson KS, Timmons CF and Schneider NR (1994) Trisomy 2, trisomy 20, and del(17p) as sole chromosomal abnormalities in three cases of hepatoblastoma. Genes, Chromosomes and Cancer 11: 199–202
Wasenius VM, Jekunen A, Monni O, Joensuu H, Aebi S, Howell SB and Knuutila S (1997) Comparative genomic hybridization analysis of chromosomal changes occurring during development of acquired resistance to cisplatin in human ovarian carcinoma cells. Genes, Chromosomes and Cancer 18: 286–291
Weinberg AG and Finegold MJ (1983) Primary hepatic tumors of childhood. Human Pathology 14: 512–537
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Gray, S., Kytölä, S., Matsunaga, T. et al. Comparative genomic hybridization reveals population-based genetic alterations in hepatoblastomas. Br J Cancer 83, 1020–1025 (2000). https://doi.org/10.1054/bjoc.2000.1390
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DOI: https://doi.org/10.1054/bjoc.2000.1390
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