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The Case for Proteomics and Phospho‐Proteomics in Personalized Cancer Medicine

机译:个性化癌症医学中的蛋白质组学和磷酸化蛋白质组学案例

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摘要

The concept of personalized medicine is predominantly been pursued through genomic and transcriptomic technologies, leading to the identification of multiple mutations in a large variety of cancers. However, it has proven challenging to distinguish driver and passenger mutations and to deal with tumor heterogeneity and resistant clonal populations. More generally, these heterogeneous mutation patterns do not in themselves predict the tumor phenotype. Analysis of the expressed proteins in a tumor and their modification states reveals if and how these mutations are translated to the functional level. It is already known that proteomic changes including posttranslational modifications are crucial drivers of oncogenesis, but proteomics technology has only recently become comparable in depth and accuracy to RNAseq. These advances also allow the rapid and highly sensitive analysis of formalin‐fixed and paraffin‐embedded biobank tissues, on both the proteome and phosphoproteome levels. In this perspective, pioneering mass spectrometry‐based proteomic studies are highlighted that pave the way toward clinical implementation. It is argued that proteomics and phosphoproteomics could provide the missing link to make omics analysis actionable in the clinic.
机译:个性化医学的概念主要是通过基因组学和转录组学技术追求的,从而导致了多种癌症中多种突变的鉴定。然而,事实证明,区分驾驶员和乘客突变以及应对肿瘤异质性和抗性克隆种群具有挑战性。更一般地,这些异质突变模式本身并不预测肿瘤表型。对肿瘤中表达的蛋白质及其修饰状态的分析揭示了这些突变是否以及如何翻译成功能水平。众所周知,包括翻译后修饰在内的蛋白质组学变化是致癌作用的关键驱动力,但是蛋白质组学技术的深度和准确性直到最近才可与RNAseq相提并论。这些进展还使得可以对蛋白质组和磷酸化蛋白质组水平的福尔马林固定和石蜡包埋的生物库组织进行快速,高度灵敏的分析。从这一角度出发,强调了基于质谱的开创性蛋白质组学研究,为临床实施铺平了道路。有人认为,蛋白质组学和磷酸化蛋白质组学可以提供缺失的联系,从而使组学分析在临床上可行。

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