文章：

胃癌的基因组迁移图谱

Mapping the genomic diaspora of gastric cancer

原文发布日期：2021-10-26

DOI: 10.1038/s41568-021-00412-7

类型: Review Article

开放获取: 否

英文摘要：

Gastric cancer (GC) is a leading contributor to global cancer incidence and mortality. Pioneering genomic studies, focusing largely on primary GCs, revealed driver alterations in genes such as ERBB2, FGFR2, TP53 and ARID1A as well as multiple molecular subtypes. However, clinical efforts targeting these alterations have produced variable results, hampered by complex co-alteration patterns in molecular profiles and intra-patient genomic heterogeneity. In this Review, we highlight foundational and translational advances in dissecting the genomic cartography of GC, including non-coding variants, epigenomic aberrations and transcriptomic alterations, and describe how these alterations interplay with environmental influences, germline factors and the tumour microenvironment. Mapping of these alterations over the GC life cycle in normal gastric tissues, metaplasia, primary carcinoma and distant metastasis will improve our understanding of biological mechanisms driving GC development and promoting cancer hallmarks. On the translational front, integrative genomic approaches are identifying diverse mechanisms of GC therapy resistance and emerging preclinical targets, enabled by technologies such as single-cell sequencing and liquid biopsies. Validating these insights will require specifically designed GC cohorts, converging multi-modal genomic data with longitudinal data on therapeutic challenges and patient outcomes. Genomic findings from these studies will facilitate ‘next-generation’ clinical initiatives in GC precision oncology and prevention.

摘要翻译： 

胃癌是全球癌症发病率和死亡率的主要诱因之一。开创性的基因组研究主要聚焦于原发性胃癌，揭示了ERBB2、FGFR2、TP53和ARID1A等基因的驱动突变以及多种分子亚型。然而，针对这些突变的临床治疗因分子谱中复杂的共突变模式及患者个体内的基因组异质性而效果不一。本综述重点阐述了在解析胃癌基因组图谱方面的基础与转化研究进展，包括非编码变异、表观基因组异常和转录组改变，并探讨了这些改变与环境影响、种系因素及肿瘤微环境之间的相互作用。通过绘制正常胃组织、化生、原发性癌灶和远处转移过程中胃癌生命周期的基因变异图谱，将深化我们对驱动胃癌发展及促进癌症特征形成的生物学机制的理解。在转化研究方面，借助单细胞测序和液体活检等技术，整合基因组方法正在识别胃癌治疗耐药性的多种机制及新兴的临床前靶点。验证这些发现需要专门设计的胃癌队列研究，将多模态基因组数据与治疗挑战及患者预后的纵向数据相整合。这些研究获得的基因组发现将推动胃癌精准肿瘤学与预防领域的"下一代"临床计划。

原文链接：

Mapping the genomic diaspora of gastric cancer