Foundation Medicine, Inc., Cambridge, Massachusetts.
Foundation Medicine, Inc., Cambridge, Massachusetts.
J Thorac Oncol. 2019 Feb;14(2):255-264. doi: 10.1016/j.jtho.2018.10.008. Epub 2018 Oct 24.
Genomic profiling informs selection of matched targeted therapies as part of routine clinical care in NSCLC. Tissue biopsy is the criterion standard; however, genomic profiling of blood-derived circulating tumor DNA (ctDNA) has emerged as a minimally invasive alternative.
Hybrid capture-based genomic profiling of 62 genes was performed on blood-based ctDNA from 1552 patients with NSCLC.
Evidence of ctDNA was detected in 80% of samples, and in 86% of these cases, at least one reportable genomic alteration (GA) was detected. Frequently altered genes were tumor protein p53 gene (TP53) (59%), EGFR (25%), and KRAS (17%). Comparative analysis with a tissue genomic database (N = 21,500) showed similar frequencies of GAs per gene, although KRAS mutation and EGFR T790M were more frequent in tissue and ctDNA, respectively (both p < 0.0001), likely reflecting the use of liquid versus tissue biopsy after relapse during targeted therapy. In temporally matched ctDNA and tissue samples from 33 patients with evidence of ctDNA in their blood, 64% of GAs detected in tissue were also detected in ctDNA, including 78% of short variants (58 of 74) and 100% of rearrangements (four of four), but only 16% of amplifications (four of 25).
Genomic profiling of ctDNA detected clinically relevant GAs in a significant subset of NSCLC cases. Most alterations detected in matched tissue were also detected in ctDNA. These results suggest the utility of ctDNA testing in advanced NSCLC as a complementary approach to tissue testing. Blood-based ctDNA testing may be particularly useful at the time of progression during targeted therapy.
基因组分析可作为非小细胞肺癌常规临床护理的一部分，为匹配的靶向治疗提供信息。组织活检是标准方法；然而，血液衍生的循环肿瘤 DNA（ctDNA）的基因组分析已成为一种微创的替代方法。
对 1552 例非小细胞肺癌患者的血液 ctDNA 进行了基于杂交捕获的 62 个基因的基因组分析。
在 80%的样本中检测到了 ctDNA 的证据，在这些情况下，有 86%至少检测到了一个可报告的基因组改变（GA）。经常发生改变的基因是肿瘤蛋白 p53 基因（TP53）（59%）、EGFR（25%）和 KRAS（17%）。与组织基因组数据库（N=21500）的比较分析表明，每个基因的 GA 频率相似，尽管 KRAS 突变和 EGFR T790M 在组织和 ctDNA 中更为常见（均 p<0.0001），这可能反映了在靶向治疗后复发期间液体与组织活检的使用。在 33 例有血液 ctDNA 证据的患者的 ctDNA 和组织的时间匹配样本中，组织中检测到的 64%的 GA 也在 ctDNA 中检测到，包括 78%的短变异（58/74）和 100%的重排（4/4），但只有 16%的扩增（25/4）。
ctDNA 的基因组分析在相当一部分非小细胞肺癌病例中检测到了具有临床意义的 GA。在匹配的组织中检测到的大多数改变也在 ctDNA 中检测到。这些结果表明，ctDNA 检测在晚期非小细胞肺癌中作为组织检测的补充方法具有实用性。在靶向治疗进展期间，基于血液的 ctDNA 检测可能特别有用。
