论文标题
基因组学引导的恶性调节特征绘制了人类干细胞相关逆转录病毒序列（SCARS）和功能活性hESC增强子的关键作用
Genomics-guided drawing of malignant regulatory signatures revealed a pivotal role of human stem cell-associated retroviral sequences (SCARS) and functionally-active hESC enhancers
论文作者
论文摘要
从患者和医师的角度来看，肿瘤恶性表型的临床定义可能仅限于早期诊断出恶性肿瘤的亚型，而现有治疗失败的风险增加和癌症死亡的可能性很高。这是在此贡献中考虑对恶性监管签名的理解的观点。从实验和临床观察的角度来看，分析表明，人类干细胞相关的逆转录病毒序列（SCARS）在临床致命性恶性肿瘤的起源和病理生理学中的关键作用。疤痕代表了基因组调节序列的进化和生物学相关的家族，其主要生理功能是在人类植入前植入前胚胎发生过程中创建和维持干性表型。在细胞分化过程中，必须沉默疤痕的表达，而在大多数末期差异化的人类细胞中，在人体中执行专业功能的人类细胞中的疤痕活性保持沉默。疤痕的消除抑制和持续激活导致分化缺陷的表型，组织和器官特异性的临床表现，它们被诊断为病理状况，该病理状况由病原体，分子和遗传检查作为恶性生长的共识所定义。当代证据表明，疤痕的持续活动的高油性分子信号与数千个功能活性增强子的基因组调节网络相关联，触发下游遗传基因座的交战可能是可靠的可靠诊断工具，既可以作为可靠的分子靶标，又可以作为可识别的可识别型诊断和有效的临床治疗。
From patients and physicians perspectives, the clinical definition of a tumor malignant phenotype could be restricted to the early diagnosis of sub-types of malignancies with the increased risk of existing therapy failure and high likelihood of death from cancer. It is the viewpoint from which the understanding of malignant regulatory signatures is considered in this contribution. Analyses from this perspective of experimental and clinical observations revealed the pivotal role of human stem cell-associated retroviral sequences (SCARS) in the origin and pathophysiology of clinically-lethal malignancies. SCARS represent evolutionary- and biologically-related family of genomic regulatory sequences, the principal physiological function of which is to create and maintain the stemness phenotype during human preimplantation embryogenesis. SCARS expression must be silenced during cellular differentiation and SCARS activity remains silent in most terminally-differentiated human cells performing specialized functions in the human body. De-repression and sustained activation of SCARS result in differentiation-defective phenotypes, tissue- and organ-specific clinical manifestations of which are diagnosed as pathological conditions defined by a consensus of pathomorphological, molecular, and genetic examinations as the malignant growth. Contemporary evidence are presented that high-fidelity molecular signals of continuing activities of SCARS in association with genomic regulatory networks of thousands functionally-active enhancers triggering engagements of down-stream genetic loci may serve as both reliable diagnostic tools and druggable molecular targets readily amenable for diagnosis and efficient therapeutic management of clinically-lethal malignancies.
