Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings, addressing an unmet need in the diagnostic and clinical management of these patients. Despite the great diagnostic advances made in the past decade, the use of traditional diagnostic procedures only enables the tissue of origin to be determined in ∼30% of patients with CUP. Thus, development of molecularly guided diagnostic strategies has emerged to complement traditional procedures, thereby improving the clinical management of patients with CUP. In this Review, we present the latest data on strategies using epigenetics and other molecular biomarkers to guide therapeutic decisions involving patients with CUP, and we highlight areas warranting further research to engage the medical community in this unmet need.

表观遗传学改变是人类癌症的共同特征。单一表观遗传标记已开始纳入临床实践。但是，这些生物标志物的翻译用途尚未在“组学”水平上得到验证。患有原发性未知癌症（CUP）的患者的起源组织的鉴定是如何将表观基因组学纳入临床环境的一个例子，解决了这些患者的诊断和临床管理中未满足的需求。尽管在过去十年中取得了巨大的诊断进展，但使用传统的诊断程序只能使〜30％的银联患者。因此，已经出现了分子指导的诊断策略的发展以补充传统方法，从而改善了CUP患者的临床管理。在本综述中，我们提供了使用表观遗传学和其他分子生物标记物指导涉及CUP患者的治疗决策的策略的最新数据，并且我们重点介绍了值得进一步研究的领域，以使医学界参与这一未满足的需求。