Unique DNA methylation loci distinguish anatomic site and HPV status in head and neck squamous cell carcinoma.
Unique DNA methylation loci distinguish anatomic site and HPV status in head and neck squamous cell carcinoma.
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DOI：
10.1158/1078-0432.ccr-12-3280
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发表时间：
2013-10-01
期刊：
影响因子：
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通讯作者：
Belbin TJ
中科院分区：
文献类型：
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作者：
Lleras RA;Smith RV;Adrien LR;Schlecht NF;Burk RD;Harris TM;Childs G;Prystowsky MB;Belbin TJ
我们利用全基因组方法来鉴定在头颈鳞状细胞癌 (HNSCC) 的不同解剖部位以及可能与口咽部 HPV 状态相关的新型差异甲基化 CpG 二核苷酸。我们使用 Illumina HumanMmethylation27 珠芯片对来自 118 名在纽约州布朗克斯 Montefiore 医疗中心接受治疗的 HNSCC 患者的原发性肿瘤样本和相应的邻近粘膜进行了全基因组 DNA 甲基化分析。对于每个匹配的组织集，我们使用甲基化水平（M 值）的变化来测量差异甲基化的 CpG 位点。当按原发肿瘤的解剖部位对数据集进行单独分析时，我们在口腔 SCC 中鉴定出 293 个差异甲基化 CpG 位点，在喉 SCC 中鉴定出 219 个差异甲基化 CpG 位点，在口咽 SCC 中鉴定出 460 个差异甲基化 CpG 位点。这些差异甲基化 CpG 位点的一个子集在 HNSCC 的所有解剖部位中都很常见。按 HPV 状态分层显示 HPV 阳性患者中差异甲基化 CpG 位点的数量显着增加。来自临床 HNSCC 标本的新型表观遗传生物标志物可用作该疾病的分子分类器，揭示了该疾病的许多新研究途径。
We have utilized a genome-wide approach to identify novel differentially methylated CpG dinucleotides that are seen in different anatomic sites of head and neck squamous cell carcinoma (HNSCC), as well as those that might be related to HPV status in the oropharynx. We performed genome-wide DNA methylation profiling of primary tumor samples and corresponding adjacent mucosa from 118 HNSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M-value). When datasets were individually analyzed by anatomic site of the primary tumor, we identified 293 differentially methylated CpG loci in oral cavity SCC, 219 differentially methylated CpG loci in laryngeal SCC, and 460 differentially methylated in oropharyngeal SCC. A subset of these differentially methylated CpG loci was common across all anatomic sites of HNSCC. Stratification by HPV status revealed a significantly higher number of differentially methylated CpG loci in HPV-positive patients. Novel epigenetic biomarkers derived from clinical HNSCC specimens can be used molecular classifiers of this disease, revealing many new avenues of investigation for this disease.