Liverpool Cancer Research UK Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, Block C, Waterhouse Buildings, Brownlow Street, University of Liverpool, Liverpool L69 3GL, UK.
Br J Cancer. 2013 Feb 5;108(2):370-9. doi: 10.1038/bjc.2012.568. Epub 2013 Jan 3.
There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs.
DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival.
Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between 'CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series.
Although OSCC seems as much an 'epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.
专门针对口腔鳞状细胞癌（OSCC）的甲基化阵列数据相对较少。本研究旨在比较大肿瘤/正常配对队列中的 DNA 甲基组。
从 44 例 OSCC 和配对的正常粘膜中提取 DNA。采用 Illumina GoldenGate 高通量阵列进行 DNA 甲基化分析，该阵列包含从 807 个受表观遗传调控的基因中选择的 1505 个 CpG 位点。将这些数据与囊外扩散（ECS）、人乳头瘤病毒（HPV）状态、复发和 5 年生存率相关联。
一些基因的差异甲基化水平区分了肿瘤组织样本和匹配的正常组织。确定了 ECS 和复发的假定甲基化特征。我们的数据支持 OSCC 中“共甲基化”或 CpG 岛甲基化表型（CIMP）的概念，与更差的预后相关。还观察到 OSCC 中 NOTCH4 信号的表观遗传失调，这可能是复发的甲基化特征之一，与最近在 HNSCC 中发现的 NOTCH 突变相似。在 HPV 驱动的病例中观察到甲基化差异，但与最近在其他系列中提出的差异相比，这些差异较小。
尽管 OSCC 似乎是一种“表观遗传”疾病，但癌症表观遗传学的转化潜力尚未得到充分利用。这些数据表明可以应用现有的表观遗传生物标志物和靶点来进一步开发 OSCC 的治疗方法。
