Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Rev Genet. 2021 Aug;22(8):483-501. doi: 10.1038/s41576-021-00338-8. Epub 2021 Mar 24.
Technological innovation and rapid reduction in sequencing costs have enabled the genomic profiling of hundreds of cancer-associated genes as a component of routine cancer care. Tumour genomic profiling can refine cancer subtype classification, identify which patients are most likely to benefit from systemic therapies and screen for germline variants that influence heritable cancer risk. Here, we discuss ongoing efforts to enhance the clinical utility of tumour genomic profiling by integrating tumour and germline analyses, characterizing allelic context and identifying mutational signatures that influence therapy response. We also discuss the potential clinical utility of more comprehensive whole-genome and whole-transcriptome sequencing and ultra-sensitive cell-free DNA profiling platforms, which allow for minimally invasive, serial analyses of tumour-derived DNA in blood.
技术创新和测序成本的快速降低使得对数百个与癌症相关的基因进行基因组分析成为常规癌症治疗的一个组成部分。肿瘤基因组分析可以细化癌症亚型分类，确定哪些患者最有可能从系统治疗中获益，并筛选影响遗传性癌症风险的种系变异。在这里，我们讨论了通过整合肿瘤和种系分析、描述等位基因背景和确定影响治疗反应的突变特征来提高肿瘤基因组分析临床实用性的正在进行的努力。我们还讨论了更全面的全基因组和全转录组测序和超高灵敏度游离 DNA 分析平台的潜在临床实用性，这些平台允许对血液中的肿瘤衍生 DNA 进行微创、连续分析。
