Chromosomal Instability in Gastric Cancer Biology.
Chromosomal Instability in Gastric Cancer Biology.
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DOI：
10.1016/j.neo.2017.02.012
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Röcken C
中科院分区：
文献类型：
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作者：
Maleki SS;Röcken C
胃癌（GC）是世界上第五大常见癌症，占癌症总发病率的7%。在西方国家，由于诊断较晚，胃癌的预后很差：大约70%的患者在初次诊断后5年内死亡。最近，综合基因组分析导致GC的分子分类分为四种亚型，即微卫星不稳定型，Epstein-Barr病毒阳性型，染色体不稳定型（CIN）和基因组稳定型。胃癌的分子分类提高了我们对胃癌生物学的认识，并可能对诊断和患者治疗产生影响。微卫星不稳定GC和Epstein-Barr病毒阳性GC的诊断或多或少直截了当。微卫星不稳定性可以通过免疫组织化学（MLH1、PMS2、MSH2和MSH6）和/或分子生物学分析来检测。Epstein-Barr病毒阳性GC可通过原位杂交（Epstein-Barr病毒编码小RNA）进行检测。然而，对于CIN，测试可能更复杂，可能需要对导致CIN的潜在机制有更深入的了解。此外，CIN GC可能不构成一个独特的亚组，而可能是一个更异质性的肿瘤组的集合。在这篇综述中，我们旨在澄清CIN的定义，并指出导致这种分子表型的分子机制以及表征这种类型癌症所面临的挑战。
Gastric cancer (GC) is the fifth most common cancer in the world and accounts for 7% of the total cancer incidence. The prognosis of GC is dismal in Western countries due to late diagnosis: approximately 70% of the patients die within 5 years following initial diagnosis. Recently, integrative genomic analyses led to the proposal of a molecular classification of GC into four subtypes, i.e.,microsatellite-instable, Epstein-Barr virus–positive, chromosomal-instable (CIN), and genomically stable GCs. Molecular classification of GC advances our knowledge of the biology of GC and may have implications for diagnostics and patient treatment. Diagnosis of microsatellite-instable GC and Epstein-Barr virus–positive GC is more or less straightforward. Microsatellite instability can be tested by immunohistochemistry (MLH1, PMS2, MSH2, and MSH6) and/or molecular-biological analysis. Epstein-Barr virus–positive GC can be tested by in situ hybridization (Epstein-Barr virus encoded small RNA). However, with regard to CIN, testing may be more complicated and may require a more in-depth knowledge of the underlying mechanism leading to CIN. In addition, CIN GC may not constitute a distinct subgroup but may rather be a compilation of a more heterogeneous group of tumors. In this review, we aim to clarify the definition of CIN and to point out the molecular mechanisms leading to this molecular phenotype and the challenges faced in characterizing this type of cancer.