Interrogating the genomics of circulating tumor DNA (ctDNA; the liquid biopsy) has advantages in patients in whom tissue biopsy is difficult. However, the reported concordance between genomic analysis of tissue DNA and ctDNA is variable among studies. Herein, we characterized the clinical implications of the relationship between mutations in TP53 genes in tissue DNA versus ctDNA. The molecular profiles of both liquid (Guardant Health) and tissue (Foundation Medicine) biopsies from 433 patients were analyzed (pan-cancer setting). In 71/433 (16%) cases, all same TP53 mutations were detected in both tissue DNA and ctDNA; in 18/433 (4%), same mutation plus additional mutation/mutations; and in 27/433 (6%), different TP53 mutations were detected. In 99/433 (23%) cases, TP53 mutations were detected only in tissue DNA; in 43/433 (10%), only in ctDNA; and in 175/433 (40%), no TP53 mutations were detected in either test. When TP53 mutations were identical in tissue and ctDNA, the alterations were enriched for nonsense mutations, and survival was significantly shorter in multivariate analysis (as compared with different mutations in ctDNA vs. tissue or no mutations); this finding was independent of tumor type, time interval between tests, and the %ctDNA for TP53 mutations. In summary, in 16% of 433 patients with diverse cancers, TP53 mutations were identical in tissue DNA and ctDNA. In these individuals, the alterations were enriched for stop–gain (nonsense) mutations (results in a premature termination codon). Though unknown confounders cannot be ruled out, these patients fared significantly worse than those whose ctDNA and tissue DNA harbored different TP53 mutation portfolios or no TP53 mutations.

中文翻译：

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组织与循环肿瘤 DNA TP5​​3 突变之间关系的生存意义——来自真实世界精准医学队列的视角

询问循环肿瘤 DNA（ctDNA；液体活检）的基因组学对于组织活检困难的患者具有优势。然而，所报告的组织 DNA 和 ctDNA 基因组分析之间的一致性在不同研究中存在差异。在此，我们描述了组织 DNA 与 ctDNA 中 TP53 基因突变之间关系的临床意义。分析了来自 433 名患者的液体（Guardant Health）和组织（Foundation Medicine）活检的分子谱（泛癌设置）。在 71/433 (16%) 例中，在组织 DNA 和 ctDNA 中检测到所有相同的 TP53 突变；在 18/433 (4%) 中，相同的突变加上额外的突变/突变；在 27/433 (6%) 中，检测到不同的 TP53 突变。在 99/433 (23%) 例中，仅在组织 DNA 中检测到 TP53 突变；在 43/433 (10%) 中，仅在 ctDNA 中；在 175/433 (40%) 中，在任一测试中均未检测到 TP53 突变。当组织和 ctDNA 中的 TP53 突变相同时，这些改变富含无义突变，多变量分析中的生存期显着缩短（与 ctDNA 中的不同突变与组织或无突变相比）；这一发现与肿瘤类型、测试之间的时间间隔以及 TP53 突变的 ctDNA 百分比无关。总之，在 433 名患有不同癌症的患者中，16% 的 TP53 突变在组织 DNA 和 ctDNA 中是相同的。在这些个体中，停止增益（无义）突变（导致过早终止密码子）的改变丰富了。虽然不能排除未知的混杂因素，