从遗传异质性认识口腔鳞癌的侵袭过程

Understanding oral cancer invasion from the perspective of genetic heterogeneity

口腔鳞癌侵袭前沿是肿瘤侵袭过程中形成的具有特征性病理结构的肿瘤区域。理解肿瘤的侵袭过程,可以通过研究侵袭前沿的形成过程来实现。侵袭前沿和肿瘤内部之间存在遗传异质性,肿瘤区域之间存在一定的克隆进化关系。在遗传学水平认识肿瘤侵袭,有赖于对侵袭前沿和肿瘤内部之间克隆结构组成及克隆进化关系的揭示。在此过程中,还可获知在肿瘤侵袭中发挥重要作用的遗传学事件,这些遗传学事件可能成为潜在的治疗靶点或侵袭相关生物标志物。口腔鳞癌侵袭过程的克隆演化路径具有肿瘤间异质性,对其他癌种的相关研究也发现了这种肿瘤间异质性,进一步揭示了侵袭相关亚克隆的遗传演化及亚克隆间的相互作用。本文着眼于从遗传学角度揭示口腔鳞癌的侵袭过程,结合其他癌种的相关研究,对肿瘤侵袭过程中的关键遗传学事件、遗传异质性以及克隆演进做一综述。

The invasive front of oral cancer is a region characterized by detached mesenchymal-like tumor cells or cell groups.The process of the formation of the invasive front should be interrogated in order to understand tumor invasion.A certain degree of intratumor heterogeneity and clonal relationship exists between the tumor body and the invasive front.Understanding tumor invasion at genetic level requires revealing the clonal structure as well as the evolutionary relation-ship between the tumor body and the invasive front.The key genetic events driving tumor invasion can also be detected by reconstructing the clonal structure of the two tumor regions,on the basis of which potential therapeutic targets or biomark-ers in invasion can be identified.The evolutionary trajectories in the invasion process of oral squamous cell carcinoma(OSCC)showed a great deal of intertumor heterogeneity.Researches in other cancers also found intertumor heterogeneity in the evolutionary patterns and further revealed the evolutionary process of invasive subclones and interactions between subclones.This review aimed at understanding tumor invasion in OSCC from a genetic perspective and extending our un-derstanding of the key genetic events,genetic heterogeneity and clonal evolution during tumor invasion through evaluation of current knowledge in tumor invasion in other cancer types.