Whole-genome sequencing either alone or in combination with whole-transcriptome sequencing has started to be used to analyze clinical tumor samples to improve diagnosis, provide risk stratification, and select patient-specific therapies. Compared with current genomic testing strategies, largely focused on small number of genes tested individually or targeted panels, whole-genome and transcriptome sequencing (WGTS) provides novel opportunities to identify and report a potentially much larger number of actionable alterations with diagnostic, prognostic, and/or predictive impact. Such alterations include point mutations, indels, copy- number aberrations and structural variants, but also germline variants, fusion genes, noncoding alterations and mutational signatures. Nevertheless, these comprehensive tests are accompanied by many challenges ranging from the extent and diversity of sequence alterations detected by these methods to the complexity and limited existing standardization in interpreting them. We describe the challenges of WGTS interpretation and the opportunities with comprehensive genomic testing.

全基因组测序无论是单独使用还是与全转录组测序相结合，已开始用于分析临床肿瘤样本，以改善诊断、提供风险分层并选择患者特异性疗法。与当前的基因组测试策略（主要集中于单独测试的少量基因或目标组）相比，全基因组和转录组测序（WGTS）提供了新的机会来识别和报告潜在大量可操作的改变，包括诊断、预后和诊断。 /或预测影响。这些改变包括点突变、插入缺失、拷贝数畸变和结构变异，还包括种系变异、融合基因、非编码改变和突变特征。然而，这些综合测试伴随着许多挑战，从这些方法检测到的序列改变的程度和多样性到解释它们的复杂性和有限的现有标准化。我们描述了 WGTS 解释的挑战和全面基因组测试的机遇。