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DNA Damage Is a Potential Marker for TP53 Mutation in Colorectal Carcinogenesis

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Abstract

Purpose

The ability to measure oxidative DNA damage in a tissue allows establishment of the relationship between DNA damage and mutations in normal and neoplastic cells. It is well known that TP53 is a key inhibitor of tumor development and preserves the genome integrity in each cell. The aim of the present study was to investigate the relationship between DNA damage and TP53 mutation in colorectal adenoma and adenocarcinoma, and the value of DNA damage as potential marker of TP53 mutation in non-tumor tissues adjacent to colon malignant lesions.

Methods

Tissue samples were obtained by colonoscopy from patients with adenoma and/or adenocarcinoma and from healthy volunteers. Diagnosis was defined by histopathology. Immunohistochemistry with computer-assisted image analysis was performed to quantify TP53 mutation. Oxidative DNA damage was determined by comet assay. Statistical analyses were performed with 5 % of significance level.

Results

The TP53 level was higher in non-tumor tissues from tumor patients than in normal tissues from healthy volunteers (p = 0.01). Likewise, higher TP53 levels were observed in tumor tissues compared with the non-tumor tissues (p = 0.00). Oxidative DNA damage levels were higher in tumor tissues than in non-tumor tissues (p = 0.00). The amount of TP53 (p = 0.00) and oxidative DNA damage (p = 0.00) in normal and tumor tissue was related. The relationship between oxidative DNA damage and TP53 mutation was demonstrated in all samples (p = 0.00).

Conclusion

Oxidative DNA damage is an intervening variable for TP53 mutation in colorectal adenoma-carcinoma. Our data suggests that oxidative DNA damage is a potential marker of TP53 mutation in colorectal carcinogenesis.

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Acknowledgments

The authors thank FAPESP-Sao Paulo Research Foundation (Project number 2007/01196-5 and 2011/04634-1) for financial support.

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Authors and Affiliations

  1. Postgraduate Programme Strictu Senso in Health Science, Sao Francisco University Medical School, Sao Paulo, Brazil

    José Ricardo Scalise, Regina Caeli Guerra Poças, Marcelo Lima Ribeiro & Denise Gonçalves Priolli

  2. Scientific Initiation Student, Scientific Initiation Programme, Sao Francisco University Medical School, Sao Paulo, Brazil

    Thamy Pelatieri Caneloi, Camila Oliveira Lopes, Danilo Toshio Kanno, Mayara Gonçalves Marques, Júlio Cesar Martins Valdivia & Felipe Rodrigues Maximo

  3. Department of Pathology, Sao Francisco University Medical School, Sao Paulo, Brazil

    José Aires Pereira

  4. Rua São Vicente 614. Jardim Paulista, Atibaia, SP, Brazil, CEP: 12947-390

    Denise Gonçalves Priolli

Authors
  1. José Ricardo Scalise
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  2. Regina Caeli Guerra Poças
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  3. Thamy Pelatieri Caneloi
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  8. Felipe Rodrigues Maximo
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Corresponding author

Correspondence to Denise Gonçalves Priolli.

Ethics declarations

Approval to carry out the present study was obtained from the Research Ethics Committee at São Francisco University (protocol number: 0219.0.142.000-10) and in accordance with the Helsinki Declaration of 1975, as revised in 1983. All the patients signed a free and informed consent statement after receiving information about all the stages of the study.

Conflicts of Interest

The authors declare that they have no conflict of interest.

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Scalise, J.R., Poças, R.C.G., Caneloi, T.P. et al. DNA Damage Is a Potential Marker for TP53 Mutation in Colorectal Carcinogenesis. J Gastrointest Canc 47, 409–416 (2016). https://doi.org/10.1007/s12029-016-9846-0

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  • DOI: https://doi.org/10.1007/s12029-016-9846-0

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