Homeobox gene amplification and methylation in oral squamous cell carcinoma

Maria Fernanda Setúbal Destro Rodrigues; Flávia Caló Aquino Xavier; Carina Duarte Esteves; Rebeca Barros Nascimento; Juliana Stephan Nobile; Patrícia Severino; Rafael de Cicco; Tatiana Natasha Toporcov; Eloiza Helena Tajara; Fábio Daumas Nunes

doi:10.1016/j.archoralbio.2021.105195

Homeobox gene amplification and methylation in oral squamous cell carcinoma

Arch Oral Biol. 2021 Sep:129:105195. doi: 10.1016/j.archoralbio.2021.105195. Epub 2021 Jun 8.

Affiliations

¹ Postgraduate Program in Biophotonics Applied to Health Sciences, Nove De Julho University (UNINOVE), São Paulo, SP, Brazil.
² Laboratory of Oral Surgical Pathology, School of Dentistry, Federal University of Bahia, Salvador, Brazil.
³ Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil.
⁴ Center for Experimental Research, Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
⁵ Arnaldo Vieira de Carvalho Cancer Institute, Brazil.
⁶ Departament de Epidemiology, Health Public School, University of São Paulo, São Paulo, Brazil.
⁷ Department of Molecular Biology, School of Medicine of São José do Rio Preto/FAMERP, São José do Rio Preto, SP, Brazil.
⁸ Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil. Electronic address: fadnunes@usp.br.

PMID: 34126417
DOI: 10.1016/j.archoralbio.2021.105195

Abstract

Objectives: Investigate the DNA copy number and the methylation profile of the homeobox genes HOXA5, HOXA7, HOXA9, HOXB5, HOXB13, HOXC12, HOXC13, HOXD10, HOXD11, IRX4 and ZHX1, and correlate them with clinicopathological parameters and overall survival.

Material and methods: DNA from OSCC samples and surgical margins were submitted to DNA amplification by qPCR and to DNA methylation analysis using a DNA Methylation PCR Array System.

Results: HOXA5, HOXB5 and HOXD10 were amplified in surgical margins while HOXA9, HOXB13 and IRX4 were amplified in OSCC. HOXD10 demonstrated hypermethylation in half of the tumor while ZHX1 did not show hypermethylation. No correlation of DNA copy number or methylation with clinicopathological parameters or survival was observed.

Conclusion: HOXA9, HOXB13 and IRX4 genes appears to be regulated by amplification and HOXD10 by methylation in OSCC. Further studies are needed to determine the role of these events in OSCC development.

Keywords: DNA methylation; Gene amplification; Homeobox genes; Oral squamous cell carcinoma.

MeSH terms

Biomarkers, Tumor
Carcinoma, Squamous Cell* / genetics
DNA Methylation
Gene Amplification
Gene Expression Regulation, Neoplastic
Genes, Homeobox / genetics
Head and Neck Neoplasms*
Humans
Mouth Neoplasms* / genetics
Promoter Regions, Genetic
Squamous Cell Carcinoma of Head and Neck

Substances

Biomarkers, Tumor