Epigenetic alterations in head and neck cancer : a brief update

Hellquist, Henrik (author), Castelo-Branco, Pedro (author), Stenman, Göran (author), Nadal, Alfons (author), Agaimy, Abbas (author), Zidar, Nina (author), Lima-Souza, Reydson Alcides de (author), Mariano, Fernanda Viviane (author), Coca-Pelaz, Andrés (author), Ferlito, Alfio (author)

DNA methylation of tumour suppressor genes is the most well-studied epigenetic alterations in head and neck cancer. The tumour suppressor genes CDKN2A, RASSF1, and TIMP3 are the most frequently investigated, but the methylation status has been analysed in more than another dozen genes, for example MGMT. In oral squamous cell carcinoma (OSCC) methylation of MGMT, DAPK, and CDKN2A are promising biomarkers of prognostic value. Inhibition of LSD1, encoding a histone demethylase, attenuates the development and growth of OSCC. Methylation of TIMP3 in sinonasal adenocarcinoma (intestinal type) is associated with a significant worse survival, an association not seen in sinonasal squamous cell carcinoma. Olfactory neuroblastoma can be distinguished into four unique subgroups by methylation profiling. Methylation of RASSF1 is seen in NUT carcinoma, and significantly higher RASSF1 methylation is found in SMARCB1/INI1-deficient tumours compared to the less aggressive SMARCB1/INI-proficient tumours. Genome-wide methylation profiling in combination with IDH2 mutation status suggests that tumours with undifferentiable SNUC morphology can be classified into for subgroups. Most salivary gland carcinoma subtypes have specific epigenetic signatures. Four of the most common subtypes, adenoid cystic carcinoma (ADCC), mucoepidermoid carcinoma (MEC), acinic cell carcinoma (ACC), and carcinoma ex pleomorphic adenoma (CXPA) have all methylation of RASSF1A, two (MEC and ADCC) also of TIMP3 and two (MEC and CXPA) of p16INK4a. A methylation landscape of 20 salivary gland tumours (SGTs) is nowadays available.

• Language: English
• Keywords: clinical implications, epigenetics, head and neck cancer, methylation, tumour suppressor genes
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: Str. 289–295
• Numbering: Vol. 489, iss. 2
• PID: 20.500.12556/RUL-186737
• UDC: 616-006
• ISSN on article: 1432-2307
• DOI: 10.1007/s00428-026-04528-9
• COBISS.SI-ID: 281121795
• Publication date in RUL: 04.09.2026

Record is a part of a journal

• Title: Virchows archiv
• Publisher: Springer Link
• ISSN: 1432-2307
• COBISS.SI-ID: 2517524

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: klinični izid, epigenetika, novotvorbe glave in vratu, metilacija, geni za zaviranje tumorjev