Abstract:
Strong epigenetic pan-cancer biomarkers are required to meet several current, urgent clinical needs and to further improve the present chemotherapeutic standard. We have concentrated on the investigation of epigenetic alteration of the hTERT gene, which is frequently epigenetically dysregulated in a number of cancers in specific developmental stages. Distinct DNA methylation profiles were identified in our data on early urothelial cancer. An efficient EpihTERT assay could be developed utilizing suitable combinations with sequence-dependent thermodynamic parameters to distinguish between differentially methylated states. We infer from this data set, the epigenetic context, and the related literature that a CpG-rich, 2800 bp region, a prominent CpG island, surrounding the transcription start of the hTERT gene is the crucial epigenetic zone for the development of a potent biomarker. In order to accurately describe this region, we have named it \"Acheron\" (Ἀχέρων). In Greek mythology, this is the river of woe and misery and the path to the underworld. Exploitation of the DNA methylation profiles focused on this region, e.g., idiolocal normalized Methylation Specific PCR (IDLN-MSP), opens up a wide range of new possibilities for diagnosis, determination of prognosis, follow-up, and detection of residual disease. It may also have broad implications for the choice of chemotherapy.
摘要:
强大的表观遗传泛癌症生物标志物需要满足几个当前,迫切需要临床上进一步完善目前的化疗标准。我们集中研究了hTERT基因的表观遗传改变,在许多处于特定发育阶段的癌症中,它经常在表观遗传上失调。在我们关于早期尿路上皮癌的数据中发现了不同的DNA甲基化谱。可以利用与序列相关的热力学参数的合适组合来开发有效的EpihTERT测定,以区分差异甲基化状态。我们从这个数据集推断,表观遗传背景,以及相关文献表明,富含CpG的人,2800bp区域,一个著名的CpG岛,围绕hTERT基因的转录起点是开发有效生物标志物的关键表观遗传区。为了准确地描述这个地区,我们将其命名为“Acheron”(χρων)。在希腊神话中,这是灾难和苦难的河流,也是通往黑社会的道路。利用DNA甲基化谱集中在这个区域,例如,特殊标准化甲基化特异性PCR(IDLN-MSP),为诊断开辟了广泛的新可能性,预后的确定,后续行动,和残留疾病的检测。它也可能对化疗的选择有广泛的影响。