Authors' Affiliations: Departments of Pathology; Epidemiology & Population Health; Pediatrics, Microbiology & Immunology; Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine; and Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center, Medical Arts Pavilion, Bronx, New York.
Clin Cancer Res. 2013 Oct 1;19(19):5444-55. doi: 10.1158/1078-0432.CCR-12-3280. Epub 2013 Jul 26.
We have used 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 conducted 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 squamous cell carcinoma (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+ patients.
Novel epigenetic biomarkers derived from clinical HNSCC specimens can be used as molecular classifiers of this disease, revealing many new avenues of investigation for this disease.
我们采用全基因组方法鉴定了头颈部鳞状细胞癌（HNSCC）不同解剖部位出现的新型差异甲基化 CpG 二核苷酸，以及那些可能与口咽 HPV 状态相关的 CpG 二核苷酸。
我们使用 Illumina HumanMethylation27 珠芯片对来自纽约布朗克斯蒙蒂菲奥里医疗中心的 118 名接受治疗的 HNSCC 患者的原发性肿瘤样本和相应的相邻黏膜进行了全基因组 DNA 甲基化谱分析。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。
当单独按原发性肿瘤的解剖部位分析数据集时，我们在口腔鳞状细胞癌（SCC）中鉴定出 293 个差异甲基化 CpG 位点，在喉鳞状细胞癌中鉴定出 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 位点中的一部分在 HNSCC 的所有解剖部位都很常见。HPV 状态分层显示 HPV+患者中差异甲基化 CpG 位点的数量明显更高。
源自临床 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，为该疾病的研究开辟了许多新途径。
