Survival Implications of the Relationship between Tissue versus Circulating Tumor DNA TP53 Mutations-A Perspective from a Real-World Precision Medicine Cohort. Mol Cancer Ther 2020 Dec;19(12):2612-2620
Date
10/02/2020Pubmed ID
32999047DOI
10.1158/1535-7163.MCT-20-0097Scopus ID
2-s2.0-85100512510 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
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.
Author List
Rosenberg S, Okamura R, Kato S, Soussi T, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biomarkers, TumorCirculating Tumor DNA
Humans
Mutation
Neoplasms
Precision Medicine
Prognosis
Tumor Suppressor Protein p53
