Genetics and Molecular Biology (Aug 2020)

Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma

  • Raquel Silva dos Reis,
  • Jéssica Aflávio dos Santos,
  • Priscila Marinho de Abreu,
  • Raquel Spinassé Dettogni,
  • Eldamária de Vargas Wolfgramm dos Santos,
  • Elaine Stur,
  • Lidiane Pignaton Agostini,
  • Quézia Silva Anders,
  • Lyvia Neves Rebello Alves,
  • Isabella Bittencourt do Valle,
  • Marília Arantes Lima,
  • Evandro Duccini Souza,
  • José Roberto Vasconcelos de Podestá,
  • Sandra Ventorin von Zeidler,
  • Melissa de Freitas Cordeiro-Silva,
  • Iúri Drumond Louro

DOI
https://doi.org/10.1590/1678-4685-gmb-2019-0334
Journal volume & issue
Vol. 43, no. 3

Abstract

Read online Read online

Abstract Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.

Keywords