Mani D R, Krug Karsten, Zhang Bing, Satpathy Shankha, Clauser Karl R, Ding Li, Ellis Matthew, Gillette Michael A, Carr Steven A
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Nat Rev Cancer. 2022 May;22(5):298-313. doi: 10.1038/s41568-022-00446-5. Epub 2022 Mar 2.
Genomic analyses in cancer have been enormously impactful, leading to the identification of driver mutations and development of targeted therapies. But the functions of the vast majority of somatic mutations and copy number variants in tumours remain unknown, and the causes of resistance to targeted therapies and methods to overcome them are poorly defined. Recent improvements in mass spectrometry-based proteomics now enable direct examination of the consequences of genomic aberrations, providing deep and quantitative characterization of tumour tissues. Integration of proteins and their post-translational modifications with genomic, epigenomic and transcriptomic data constitutes the new field of proteogenomics, and is already leading to new biological and diagnostic knowledge with the potential to improve our understanding of malignant transformation and therapeutic outcomes. In this Review we describe recent developments in proteogenomics and key findings from the proteogenomic analysis of a wide range of cancers. Considerations relevant to the selection and use of samples for proteogenomics and the current technologies used to generate, analyse and integrate proteomic with genomic data are described. Applications of proteogenomics in translational studies and immuno-oncology are rapidly emerging, and the prospect for their full integration into therapeutic trials and clinical care seems bright.
癌症的基因组分析产生了巨大影响，促成了驱动突变的识别和靶向治疗的发展。但是，肿瘤中绝大多数体细胞突变和拷贝数变异的功能仍然未知，对靶向治疗的耐药原因及克服耐药的方法也尚不明确。基于质谱的蛋白质组学技术的最新进展，现在能够直接检测基因组畸变的后果，对肿瘤组织进行深度定量表征。将蛋白质及其翻译后修饰与基因组、表观基因组和转录组数据相结合，构成了蛋白质基因组学这一新领域，并且已经带来了新的生物学和诊断知识，有可能增进我们对恶性转化和治疗结果的理解。在本综述中，我们描述了蛋白质基因组学的最新进展以及对多种癌症进行蛋白质基因组分析的关键发现。还介绍了与蛋白质基因组学样本的选择和使用相关的注意事项，以及用于生成、分析蛋白质组数据并将其与基因组数据整合的当前技术。蛋白质基因组学在转化研究和免疫肿瘤学中的应用正在迅速兴起，将其全面整合到治疗试验和临床护理中的前景似乎十分光明。
