研究动态
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hTERT 表观遗传学为癌症的诊断和化疗的循证指导提供了新的视角。

hTERT Epigenetics Provides New Perspectives for Diagnosis and Evidence-Based Guidance of Chemotherapy in Cancer.

发表日期:2024 Jul 04
作者: Simeon Santourlidis, Marcos J Araúzo-Bravo, Robert T Brodell, Mohamed Hassan, Marcelo L Bendhack
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

需要强大的表观遗传泛癌生物标志物来满足当前的一些紧迫的临床需求并进一步提高现有的化疗标准。我们集中研究 hTERT 基因的表观遗传改变,该基因在许多处于特定发育阶段的癌症中经常出现表观遗传失调。我们在早期尿路上皮癌的数据中发现了不同的 DNA 甲基化谱。可以利用与序列依赖性热力学参数的适当组合来开发有效的 EpihTERT 测定,以区分差异甲基化状态。我们从该数据集、表观遗传背景和相关文献中推断,hTERT 基因转录起始点周围富含 CpG 的 2800 bp 区域(一个突出的 CpG 岛)是开发有效生物标志物的关键表观遗传区域。为了准确地描述这个区域,我们将其命名为“Acheron”(Ἀχέρων)。在希腊神话中,这是痛苦和痛苦的河流,也是通往地狱的道路。利用集中于该区域的 DNA 甲基化谱,例如局部标准化甲基化特异性 PCR (IDLN-MSP),为诊断、预后确定、随访和残留疾病检测开辟了广泛的新可能性。它也可能对化疗的选择产生广泛的影响。
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.