Methylation Suicide in Cancer (PQ10)

描述（由申请人提供）：长期以来，人们一直认为肿瘤抑制基因在癌变过程中发生异常DNA甲基化转变，但没有产生生物标志物或治疗方法。我们发现，在肿瘤抑制基因的异常从头甲基化是非常罕见的，并占主导地位的异常是整个基因组的DNA甲基化的损失。虽然癌症中的去甲基化被认为是肿瘤进展的一个因素，但此处显示的数据表明，这更可能是基于甲基化的抗肿瘤系统的表现，该系统诱导肿瘤细胞凋亡并激发抗肿瘤免疫应答。对癌症基因组去甲基化的进一步研究可能会产生新的诊断和治疗方法。去甲基化发生在肿瘤发生的早期，并且有可能设计出将增强甲基化自杀途径的治疗，以降低恶性疾病的发生率或严重程度。与其他生物分子相比，DNA生物标志物检测的稳定性和灵敏度表明，通过全基因组甲基化分析鉴定DNA甲基化生物标志物可以有效地增强早期诊断。

DESCRIPTION (provided by applicant): It has long been believed that abnormal DNA methylation turns of tumor suppressor genes during carcinogenesis, but no biomarker or therapeutic approach has resulted. We find that abnormal de novo methylation at tumor suppressor genes is very rare, and that the dominant abnormality is a loss of DNA methylation across the genome. While demethylation in cancer has been regarded as a contributor to tumor progression, the data shown here indicate instead that is more likely to be a manifestation of a methylation-based antitumor system that induces apoptosis of tumor cells and elicits an antitumor immune response. Further investigation of genome demethylation in cancer may produce new approaches to diagnosis and treatment. Demethylation occurs early in tumorigenesis, and it may be possible to devise treatments that will augment the methylation suicide pathway so as to reduce the incidence or severity of malignant disease. The stability and sensitivity of detection of DNA biomarkers as compared to other biomolecules suggests that the identification of DNA methylation biomarkers through whole-genome methylation profiling could be effective in enhancing early diagnosis.