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Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas

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Abstract

Gallbladder cancer is a rare malignancy and presents a poor prognosis. MYC and p53 have been implicated in gallbladder carcinogenesis. However, little is known about the molecular mechanisms involved in their regulation in this neoplasia. Here, we evaluated the MYC and TP53 copy numbers in gallbladder tumors and their possible association with protein expression. We also investigated whether MYC may be controlled by mutations and DNA promoter methylation. In the present study, 15 samples of invasive gallbladder carcinomas and six control samples were analyzed. On the other hand, the expression of MYC and p53 was more frequent in gallbladder carcinomas than in control samples (p = 0.002, p = 0.046, respectively). Gain of copies of the MYC and TP53 genes was detected in 86.7 and 50 % of gallbladder carcinomas, respectively. MYC and TP53 amplifications were associated with immunoreactivity of their protein (p = 0.029, p = 0.001, respectively). MYC hypomethylation was only detected in tumoral samples and was associated with its protein expression (p = 0.029). MYC mutations were detected in 80 % of tumor samples. The G allele at rs117856857 was associated with the presence of gallbladder tumors (p = 0.019) and with MYC expression (p = 0.044). Moreover, two tumors presented a pathogenic mutation in MYC exon 2 (rs28933407). Our study highlights that the gain of MYC and TP53 copies seems to be a frequent finding in gallbladder cancer. In addition, gain of copies, hypomethylation and point mutations at MYC may contribute to overexpression of its protein in this type of cancer.

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Acknowledgments

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; MCS and RRB) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; MFL) as grants and fellowship awards.

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None.

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Authors and Affiliations

  1. Núcleo de Pesquisa em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, 60673-000, Brazil

    Geraldo Ishak, Ney Pereira Carneiro dos Santos, Samia Demachki, Danielle Queiroz Calcagno, Paulo Pimentel Assumpção & Rommel Rodríguez Burbano

  2. Genetics Division, Department of Morphology and Genetic, Federal University of São Paulo, R. Botucatu, 740, São Paulo, SP, CEP 04023-900, Brazil

    Mariana Ferreira Leal & Marília Cardoso Smith

  3. Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil

    Mariana Ferreira Leal

  4. Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil

    Caroline Aquino Moreira Nunes, Barbara do Nascimento Borges & Rommel Rodríguez Burbano

  5. Centro de Tecnologia Agropecuária, Instituto Socioambiental e dos Recursos Hídricos, Universidade Federal Rural da Amazônia, Belém, PA, Brazil

    Barbara do Nascimento Borges

Authors
  1. Geraldo Ishak
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  2. Mariana Ferreira Leal
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  3. Ney Pereira Carneiro dos Santos
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  4. Samia Demachki
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  6. Barbara do Nascimento Borges
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  7. Danielle Queiroz Calcagno
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  9. Paulo Pimentel Assumpção
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  10. Rommel Rodríguez Burbano
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Corresponding author

Correspondence to Mariana Ferreira Leal.

Additional information

Geraldo Ishak and Mariana Ferreira Leal have contributed equally to this work.

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Ishak, G., Leal, M.F., dos Santos, N.P.C. et al. Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas. Clin Exp Med 15, 421–426 (2015). https://doi.org/10.1007/s10238-014-0311-8

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  • DOI: https://doi.org/10.1007/s10238-014-0311-8

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