Details

Autor(en) / Beteiligte

• Soares-Lima, Sheila Coelho
• Mehanna, Hisham
• Camuzi, Diego
• de Souza-Santos, Paulo Thiago
• Simão, Tatiana de Almeida
• Nicolau-Neto, Pedro
• Almeida Lopes, Monique de Souza
• Cuenin, Cyrille
• Talukdar, Fazlur Rahman
• Batis, Nikolaos
• Costa, Izabella
• Dias, Fernando
• Degli Esposti, Davide
• Boroni, Mariana
• Herceg, Zdenko
• Ribeiro Pinto, Luis Felipe

Titel

Upper Aerodigestive Tract Squamous Cell Carcinomas Show Distinct Overall DNA Methylation Profiles and Different Molecular Mechanisms behind WNT Signaling Disruption

Ist Teil von

• Cancers, 2021-06, Vol.13 (12), p.3014

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek

Beschreibungen/Notizen

• Upper aerodigestive tract (UADT) tumors present different biological behavior and prognosis, suggesting specific molecular mechanisms underlying their development. However, they are rarely considered as single entities (particularly head and neck subsites) and share the most common genetic alterations. Therefore, there is a need for a better understanding of the global DNA methylation differences among UADT tumors. We performed a genome-wide DNA methylation analysis of esophageal (ESCC), laryngeal (LSCC), oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas, and their non-tumor counterparts. The unsupervised analysis showed that non-tumor tissues present markedly distinct DNA methylation profiles, while tumors are highly heterogeneous. Hypomethylation was more frequent in LSCC and OPSCC, while ESCC and OSCC presented mostly hypermethylation, with the latter showing a CpG island overrepresentation. Differentially methylated regions affected genes in 127 signaling pathways, with only 3.1% of these being common among different tumor subsites, but with different genes affected. The WNT signaling pathway, known to be dysregulated in different epithelial tumors, is a frequent hit for DNA methylation and gene expression alterations in ESCC and OPSCC, but mostly for genetic alterations in LSCC and OSCC. UADT tumor subsites present differences in genome-wide methylation regarding their profile, intensity, genomic regions and signaling pathways affected.