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
Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rua André Cavalcanti, 37-6° Andar, Bairro de Fátima, Rio de Janeiro 20231-050, Brazil.
Institute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Cancers (Basel). 2021 Jun 16;13(12):3014. doi: 10.3390/cancers13123014.
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.
上消化道（UADT）肿瘤表现出不同的生物学行为和预后，提示其发生发展存在特定的分子机制。然而，它们很少被视为单一实体（特别是头颈部亚部位），且具有最常见的基因改变。因此，有必要更好地了解UADT肿瘤之间的全基因组DNA甲基化差异。我们对食管鳞状细胞癌（ESCC）、喉鳞状细胞癌（LSCC）、口腔鳞状细胞癌（OSCC）和口咽鳞状细胞癌（OPSCC）及其相应的非肿瘤组织进行了全基因组DNA甲基化分析。无监督分析表明，非肿瘤组织呈现出明显不同的DNA甲基化谱，而肿瘤具有高度异质性。低甲基化在LSCC和OPSCC中更为常见，而ESCC和OSCC大多呈现高甲基化，后者显示出CpG岛的过度富集。差异甲基化区域影响127条信号通路中的基因，其中只有3.1%在不同肿瘤亚部位中是共同的，但受影响的基因不同。已知在不同上皮肿瘤中失调的WNT信号通路，在ESCC和OPSCC中是DNA甲基化和基因表达改变的常见靶点，但在LSCC和OSCC中主要是基因改变的靶点。UADT肿瘤亚部位在全基因组甲基化方面，在其谱、强度、受影响的基因组区域和信号通路方面存在差异。
