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Upregulated genes at 2q24 gains as candidate oncogenes in hepatoblastomas

    Tatiane Cristina Rodrigues

    Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil

    ,
    Felipe Fidalgo

    International Center for Research, A. C. Camargo Cancer Center, São Paulo, Brazil

    ,
    Cecilia Maria Lima da Costa

    Department of Pediatric Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil

    ,
    Elisa Napolitano Ferreira

    International Center for Research, A. C. Camargo Cancer Center, São Paulo, Brazil

    ,
    Isabela Werneck da Cunha

    Department of Pathology, A. C. Camargo Cancer Center, São Paulo, Brazil

    ,
    Dirce Maria Carraro

    International Center for Research, A. C. Camargo Cancer Center, São Paulo, Brazil

    ,
    Ana Cristina Victorino Krepischi

    Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil

    International Center for Research, A. C. Camargo Cancer Center, São Paulo, Brazil

    &
    Carla Rosenberg

    *Author for correspondence:

    E-mail Address: carlarosenberg@uol.com.br

    Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil

    Published Online:https://doi.org/10.2217/fon.14.149

    ABSTRACT 

    Aim: Cytogenetic data of hepatoblastomas, a rare embryonal tumor of the liver, mostly consist of descriptions of whole-chromosome aneuploidies and large chromosome alterations. High-resolution cytogenetics may provide clues to hepatoblastoma tumorigenesis and indicate markers with clinical significance. Patients & methods: We used array-CGH (180K) to screen for genomic imbalances in nine hepatoblastomas. Additionally, we investigated the expression pattern of selected genes exhibiting copy number changes. Results: Analysis showed mainly whole-chromosome or chromosome-arm aneuploidies, but some focal aberrations were also mapped. Expression analysis of 48 genes mapped at one 10 Mb amplification at 2q24 revealed upregulation of DAPL1, ERMN, GALNT5, SCN1A and SCN3A in the set of tumors compared with differentiated livers. Conclusion: These genes appear as candidates for hepatoblastoma tumorigenesis.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Howlader N, Noone AM, Krapcho M, Neyman M, Aminou R. SEER Cancer Statistics Review, 1975–2008. National Cancer Institute, Bethesda, MD, USA (2011).Google Scholar
    • 2 Isaacs H Jr. Fetal and neonatal hepatic tumors. J. Pediatr. Surg. 42(11), 1797–1803 (2007).Crossref, MedlineGoogle Scholar
    • 3 Rougemont AL, McLin VA, Toso C, Wildhaber B E. Adult hepatoblastoma: learning from children. J. Hepatol. 56(6), 1392–1403 (2012).Crossref, MedlineGoogle Scholar
    • 4 Nakamura S, Sho M, Kanehiro H, Tanaka T, Kichikawa K, Nakajima Y. Adult hepatoblastoma successfully treated with multimodal treatment. Langenbecks Arch. Surg. 395(8), 1165–1168 (2010).Crossref, MedlineGoogle Scholar
    • 5 Semeraro M, Branchereau S, Maibach R et al. Relapses in hepatoblastoma patients: clinical characteristics and outcome – experience of the International Childhood Liver Tumour Strategy Group (SIOPEL). Eur. J. Cancer 49(4), 915–922 (2013).Crossref, Medline, CASGoogle Scholar
    • 6 Kingston JE, Herbert A, Draper GJ, Mann JR. Association between hepatoblastoma and polyposis coli. Arch. Dis. Child 58(12), 959–962 (1983).Crossref, Medline, CASGoogle Scholar
    • 7 Spector LG. Birch J. The epidemiology of hepatoblastoma. Pediatr. Blood Cancer 59(5), 776–779 (2012).Crossref, MedlineGoogle Scholar
    • 8 Morland B, de Ville de Goyet J. Primary hepatic tumours. In: Diseases of the Liver and Biliary System in Children (2nd Edition). Blackwell Science, Oxford, UK (2004). Google Scholar
    • 9 Emre S, Umman V, Rodriguez-Davalos M. Current concepts in pediatric liver tumors. Pediatr. Transplant. 16(6), 549–563 (2012).Crossref, Medline, CASGoogle Scholar
    • 10 Pahlman S, Stockhausen MT, Fredlund E, Axelson H. Notch signaling in neuroblastoma. Semin. Cancer Biol. 14(5), 365–373 (2004).Crossref, Medline, CASGoogle Scholar
    • 11 Davenport KP, Blanco FC, Sandler AD. Pediatric malignancies: neuroblastoma, Wilm's tumor, hepatoblastoma, rhabdomyosarcoma, and sacroccygeal teratoma. Surg. Clin. North Am. 92(3), 745–767 (2012).Crossref, MedlineGoogle Scholar
    • 12 Armengol C, Cairo S, Fabre M, Buendia MA. Wnt signaling and hepatocarcinogenesis: the hepatoblastoma model. Int. J. Biochem. Cell Biol. 43(2), 265–270 (2011).Crossref, Medline, CASGoogle Scholar
    • 13 Scotting PJ, Walker DA, Perilongo G. Childhood solid tumours: a developmental disorder. Nat. Rev. Cancer 5(6), 481–488 (2005).Crossref, Medline, CASGoogle Scholar
    • 14 Udatsu Y, Kusafuka T, Kuroda S, Miao J, Okada A. High frequency of beta-catenin mutations in hepatoblastoma. Pediatr. Surg. Int. 17(7), 508–512 (2001).Crossref, Medline, CASGoogle Scholar
    • 15 Tomlinson GE, Kappler R. Genetics and epigenetics of hepatoblastoma. Pediatr. Blood Cancer 59(5), 785–792 (2012). • Summarizes the main findings about genetic and epigenetic profiles of hepatoblastomas, including copy number alterations.Crossref, MedlineGoogle Scholar
    • 16 Gray SG, Eriksson T, Ekstrom C et al. Altered expression of members of the IGF-axis in hepatoblastomas. Br. J. Cancer 82(9), 1561–1567 (2000).Crossref, Medline, CASGoogle Scholar
    • 17 Zatkova A, Rouillard JM, Hartmann W et al. Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma. Genes Chromosomes Cancer 39(2), 126–137 (2004).Crossref, Medline, CASGoogle Scholar
    • 18 Sugawara W, Haruta M, Sasaki F et al. Promoter hypermethylation of the RASSF1A gene predicts the poor outcome of patients with hepatoblastoma. Pediatr. Blood Cancer 49(3), 240–249 (2007).Crossref, MedlineGoogle Scholar
    • 19 Kumon K, Kobayashi H, Namiki T et al. Frequent increase of DNA copy number in the 2q24 chromosomal region and its association with a poor clinical outcome in hepatoblastoma: cytogenetic and comparative genomic hybridization analysis. Jpn J. Cancer Res. 92(8), 854–862 (2001).•• Describes the association between 2q24 cytoband gains and poor clinical outcome in hepatoblastoma.Crossref, Medline, CASGoogle Scholar
    • 20 Hu J, Wills M, Baker BA, Perlman EJ. Comparative genomic hybridization analysis of hepatoblastomas. Genes Chromosomes Cancer 27(2), 196–201 (2000).Crossref, Medline, CASGoogle Scholar
    • 21 Weber RG, Pietsch T, von Schweinitz D, Lichter P. Characterization of genomic alterations in hepatoblastomas. A role for gains on chromosomes 8q and 20 as predictors of poor outcome. Am. J. Pathol. 157(2), 571–578 (2000).Crossref, Medline, CASGoogle Scholar
    • 22 Tomlinson GE. Cytogenetics of hepatoblastoma. Front. Biosci. (Elite. Ed) 4, 1287–1292 (2012).Crossref, MedlineGoogle Scholar
    • 23 Bardi G, Johansson B, Pandis N et al. Trisomy 2 as the sole chromosomal abnormality in a hepatoblastoma. Genes Chromosomes Cancer 4(1), 78–80 (1992).Crossref, Medline, CASGoogle Scholar
    • 24 Swarts S, Wisecarver J, Bridge JA. Significance of extra copies of chromosome 20 and the long arm of chromosome 2 in hepatoblastoma. Cancer Genet. Cytogenet. 91(1), 65–67 (1996).Crossref, Medline, CASGoogle Scholar
    • 25 Schneider NR, Cooley LD, Finegold MJ, Douglass EC, Tomlinson GE. The first recurring chromosome translocation in hepatoblastoma: der(4)t(1;4)(q12;q34). Genes Chromosomes Cancer 19(4), 291–294 (1997).Crossref, Medline, CASGoogle Scholar
    • 26 Parada LA, Bardi G, Hallen M et al. Cytogenetic abnormalities and clonal evolution in an adult hepatoblastoma. Am. J. Surg. Pathol. 21(11), 1381–1386 (1997).Crossref, Medline, CASGoogle Scholar
    • 27 Sainati L, Leszl A, Stella M et al. Cytogenetic analysis of hepatoblastoma: hypothesis of cytogenetic evolution in such tumors and results of a multicentric study. Cancer Genet. Cytogenet. 104(1), 39–44 (1998).Crossref, Medline, CASGoogle Scholar
    • 28 Balogh E, Swanton S, Kiss C, Jakab ZS, Secker-Walker LM, Olah E. Fluorescence in situ hybridization reveals trisomy 2q by insertion into 9p in hepatoblastoma. Cancer Genet. Cytogenet. 102(2), 148–150 (1998).Crossref, Medline, CASGoogle Scholar
    • 29 Steenman M, Tomlinson G, Westerveld A, Mannens M. Comparative genomic hybridization analysis of hepatoblastomas: additional evidence for a genetic link with Wilms tumor and rhabdomyosarcoma. Cytogenet. Cell Genet. 86(2), 157–161 (1999).Crossref, Medline, CASGoogle Scholar
    • 30 Yeh YA, Rao PH, Cigna CT, Middlesworth W, Lefkowitch JH, Murty VV. Trisomy 1q, 2, and 20 in a case of hepatoblastoma: possible significance of 2q35-q37 and 1q12-q21 rearrangements. Cancer Genet. Cytogenet. 123(2), 140–143 (2000).Crossref, Medline, CASGoogle Scholar
    • 31 Parada LA, Limon J, Iliszko M et al. Cytogenetics of hepatoblastoma: further characterization of 1q rearrangements by fluorescence in situ hybridization: an international collaborative study. Med. Pediatr. Oncol. 34(3), 165–170 (2000).Crossref, Medline, CASGoogle Scholar
    • 32 Gray SG, Kytola S, Matsunaga T, Larsson C, Ekstrom TJ. Comparative genomic hybridization reveals population-based genetic alterations in hepatoblastomas. Br. J. Cancer 83(8), 1020–1025 (2000).Crossref, Medline, CASGoogle Scholar
    • 33 Ma SK, Cheung AN, Choy C et al. Cytogenetic characterization of childhood hepatoblastoma. Cancer Genet. Cytogenet. 119(1), 32–36 (2000).Crossref, Medline, CASGoogle Scholar
    • 34 Sandoval C, Piper J, Mowery-Rushton PA, Jayabose S. Fetal-type hepatoblastoma and del(3)(q11.2q13.2). Cancer Genet. Cytogenet. 134(2), 162–164 (2002).Crossref, Medline, CASGoogle Scholar
    • 35 Ali W, Savasan S, Rabah R, Mohamed AN. Cytogenetic findings in two new cases of hepatoblastoma. Cancer Genet. Cytogenet. 133(2), 179–182 (2002).Crossref, Medline, CASGoogle Scholar
    • 36 Surace C, Leszl A, Perilongo G, Rocchi M, Basso G, Sainati L. Fluorescent in situ hybridization (FISH) reveals frequent and recurrent numerical and structural abnormalities in hepatoblastoma with no informative karyotype. Med. Pediatr. Oncol. 39(5), 536–539 (2002).Crossref, Medline, CASGoogle Scholar
    • 37 Terracciano LM, Bernasconi B, Ruck P et al. Comparative genomic hybridization analysis of hepatoblastoma reveals high frequency of X-chromosome gains and similarities between epithelial and stromal components. Hum. Pathol. 34(9), 864–871 (2003).Crossref, Medline, CASGoogle Scholar
    • 38 Nagata T, Nakamura M, Shichino H et al. Cytogenetic abnormalities in hepatoblastoma: report of two new cases and review of the literature suggesting imbalance of chromosomal regions on chromosomes 1, 4, and 12. Cancer Genet. Cytogenet. 156(1), 8–13 (2005).Crossref, Medline, CASGoogle Scholar
    • 39 Tomlinson GE, Douglass EC, Pollock BH, Finegold MJ, Schneider NR. Cytogenetic evaluation of a large series of hepatoblastomas: numerical abnormalities with recurring aberrations involving 1q12-q21. Genes Chromosomes Cancer 44(2), 177–184 (2005).• Reports the largest cytogenetic investigation in hepatoblastomas, using classical cytogenetic techniques.Crossref, Medline, CASGoogle Scholar
    • 40 Suzuki M, Kato M, Yuyan C et al. Whole-genome profiling of chromosomal aberrations in hepatoblastoma using high-density single-nucleotide polymorphism genotyping microarrays. Cancer Sci. 99(3), 564–570 (2008).• Describes the first high-resolution investigation of copy number alterations in hepatoblastomas.Crossref, Medline, CASGoogle Scholar
    • 41 Cairo S, Armengol C, De RA et al. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 14(6), 471–484 (2008).Crossref, Medline, CASGoogle Scholar
    • 42 Stejskalova E, Malis J, Snajdauf J et al. Cytogenetic and array comparative genomic hybridization analysis of a series of hepatoblastomas. Cancer Genet. Cytogenet. 194(2), 82–87 (2009).Crossref, Medline, CASGoogle Scholar
    • 43 Terada Y, Matsumoto S, Bando K, Tajiri T. Comprehensive allelotyping of hepatoblastoma. Hepatogastroenterology 56(89), 199–204 (2009).Medline, CASGoogle Scholar
    • 44 Arai Y, Honda S, Haruta M et al. Genome-wide analysis of allelic imbalances reveals 4q deletions as a poor prognostic factor and MDM4 amplification at 1q32.1 in hepatoblastoma. Genes Chromosomes Cancer 49(7), 596–609 (2010).•• Investigation of copy number aberrations in the largest cohort of hepatoblastomas, using high-resolution technique. This study describes a high amplitude gain in an overlapped area at 2q24.Medline, CASGoogle Scholar
    • 45 SIOPEL. www.siopel.org Google Scholar
    • 46 Database of Genomic Variants. http://projects.tcag.ca/variation Google Scholar
    • 47 Human (Homo sapiens) Genome Browser Gateway. http://genome.ucsc.edu/cgi-bin/hgGateway Google Scholar
    • 48 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4), 402–408 (2001).Crossref, Medline, CASGoogle Scholar
    • 49 Evaluating reference genes expression. www.leonxie.com/referencegene.php Google Scholar
    • 50 Vandesompele J, De Preter K, Pattyn F et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3(7), RESEARCH0034 (2002).Crossref, MedlineGoogle Scholar
    • 51 Andersen CL, Jensen JL, Orntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 64(15), 5245–5250 (2004).Crossref, Medline, CASGoogle Scholar
    • 52 Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper – Excel-based tool using pair-wise correlations. Biotechnol. Lett. 26(6), 509–515 (2004).Crossref, Medline, CASGoogle Scholar
    • 53 Silver N, Best S, Jiang J, Thein SL. Selection of housekeeping genes for gene expression studies in human reticulocytes using real-time PCR. BMC Mol. Biol. 7, 33 (2006).Crossref, MedlineGoogle Scholar
    • 54 Interlogous Interaction Database. http://ophid.utoronto.ca Google Scholar
    • 55 GeneCards®. www.genecards.org Google Scholar
    • 56 Hattori K, Angel P, Le Beau MM, Karin M. Structure and chromosomal localization of the functional intronless human JUN protooncogene. Proc. Natl Acad. Sci. USA 85(23), 9148–9152 (1988).Crossref, Medline, CASGoogle Scholar