Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto.
Cancer Genomics Program, Princess Margaret Cancer Centre, University Health Network, Toronto.
Ann Oncol. 2017 May 1;28(5):946-957. doi: 10.1093/annonc/mdx023.
Following initial characterization of the reference human genome, initiatives have evolved worldwide to identify genomic aberrations in cancer with the aim of deriving diagnostic, prognostic and predictive information. However, the functional and clinical relevance of many somatic variants in cancer are presently unknown and there is no consensus definition of 'actionability' for genomic aberrancies. Therefore, while robust detection of a variety of genetic aberrations in clinical specimens remains a technical hurdle, the greater challenge lies in the interpretation of these alterations. Critical evaluation of genomic variation in cancer requires the integration of available clinical and preclinical evidence related to their frequencies, functions and roles as therapeutic targets. Many publicly accessible data resources have compiled such evidence to facilitate the understanding of genomic results and ultimately translating results to clinical action. Information for these data resources is derived from various sources including large population genomic datasets, curation of published literature, and data sharing by the scientific community. Currently, there is no widely accepted guidance to definitively assess and integrate the diagnostic, prognostic and predictive information of somatic variants using these knowledge databases. This review will describe data resources pertinent to the identification and interpretation of actionable genomic aberrations by clinicians, and highlight relevant issues in the clinical application of tumor molecular profiling results.
在初步描述了参考人类基因组后，全球范围内开展了多项举措来识别癌症中的基因组异常，旨在获取诊断、预后和预测信息。然而，目前许多癌症体细胞变异的功能和临床相关性尚不清楚，并且对于基因组异常的“可操作性”也没有共识定义。因此，虽然在临床标本中可靠地检测到各种遗传异常仍然是一个技术难题，但更大的挑战在于对这些改变的解释。癌症中基因组变异的关键评估需要整合与它们的频率、功能和作为治疗靶点的作用相关的现有临床和临床前证据。许多可公开访问的数据资源已经汇集了这些证据，以帮助理解基因组结果，并最终将结果转化为临床行动。这些数据资源的信息来自包括大型人群基因组数据集、已发表文献的编目以及科学界的数据共享等各种来源。目前，尚无广泛接受的指南来使用这些知识库明确评估和整合体细胞变异的诊断、预后和预测信息。这篇综述将描述与临床医生识别和解释可操作的基因组异常相关的数据资源，并强调肿瘤分子分析结果临床应用中的相关问题。
