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Clinical and Experimental Medicine

, Volume 15, Issue 3, pp 421–426 | Cite as

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

  • Geraldo Ishak
  • Mariana Ferreira LealEmail author
  • Ney Pereira Carneiro dos Santos
  • Samia Demachki
  • Caroline Aquino Moreira Nunes
  • Barbara do Nascimento Borges
  • Danielle Queiroz Calcagno
  • Marília Cardoso Smith
  • Paulo Pimentel Assumpção
  • Rommel Rodríguez Burbano
Letter to the Editor

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.

Keywords

Gallbladder carcinoma MYC TP53 Genetic alterations Epigenetic modifications 

Notes

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.

Conflict of interest

None.

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Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  • Geraldo Ishak
    • 1
  • Mariana Ferreira Leal
    • 2
    • 3
    Email author
  • Ney Pereira Carneiro dos Santos
    • 1
  • Samia Demachki
    • 1
  • Caroline Aquino Moreira Nunes
    • 4
  • Barbara do Nascimento Borges
    • 4
    • 5
  • Danielle Queiroz Calcagno
    • 1
  • Marília Cardoso Smith
    • 2
  • Paulo Pimentel Assumpção
    • 1
  • Rommel Rodríguez Burbano
    • 1
    • 4
  1. 1.Núcleo de Pesquisa em Oncologia, Hospital Universitário João de Barros BarretoUniversidade Federal do ParáBelémBrazil
  2. 2.Genetics Division, Department of Morphology and GeneticFederal University of São PauloSão PauloBrazil
  3. 3.Departamento de Ortopedia e TraumatologiaUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Instituto de Ciências BiológicasUniversidade Federal do ParáBelémBrazil
  5. 5.Centro de Tecnologia Agropecuária, Instituto Socioambiental e dos Recursos HídricosUniversidade Federal Rural da AmazôniaBelémBrazil

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