Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures.
Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures.
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DOI：
10.1038/s41598-017-13644-1
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发表时间：
2017-10-18
影响因子：
4.6
通讯作者：
Clifford SC
中科院分区：
文献类型：
--
作者：
Schwalbe EC;Hicks D;Rafiee G;Bashton M;Gohlke H;Enshaei A;Potluri S;Matthiesen J;Mather M;Taleongpong P;Chaston R;Silmon A;Curtis A;Lindsey JC;Crosier S;Smith AJ;Goschzik T;Doz F;Rutkowski S;Lannering B;Pietsch T;Bailey S;Williamson D;Clifford SC
快速和可靠地检测疾病相关的DNA甲基化模式具有推进分子诊断和支持研究调查的重要潜力。我们描述了最小甲基化分类器（MIMIC）的开发和验证，结合CpG签名设计从全基因组数据集，多重PCR和单碱基延伸和MALDI-TOF质谱检测，在一种新的方法来评估多位点DNA甲基化谱在常规临床适用的检测。我们说明了MIMIC的应用，成功地确定甲基化依赖的诊断分子亚组的髓母细胞瘤（最常见的恶性儿童脑肿瘤），使用很少/低质量的样本剩余的最新完成的泛欧髓母细胞瘤临床试验，难用传统的全基因组DNA甲基化分析。使用这种方法，我们确定了关键的DNA甲基化模式，从以前无法访问的队列，并揭示了新的生存差异之间的髓母细胞瘤疾病亚组具有显着的临床开发潜力。
Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.
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