Mutation-Enrichment Next-Generation Sequencing for Quantitative Detection of KRAS Mutations in Urine Cell-Free DNA from Patients with Advanced Cancers
Articolo
Data di Pubblicazione:
2017
Abstract:
Purpose: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers noninvasive biological material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRASExperimental Design: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed, and results were compared with clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer.Results: With 90 to 110 mL of urine, the KRASG12/G13 cfDNA test had an analytical sensitivity of 0.002% to 0.006% mutant copies in wild-type background. In 71 patients, the concordance between urine cfDNA and tumor was 73% (sensitivity, 63%; specificity, 96%) for all patients and 89% (sensitivity, 80%; specificity, 100%) for patients with urine samples of 90 to 110 mL. Patients had significantly fewer KRASG12/G13 copies in urine cfDNA during systemic therapy than at baseline or disease progression (P = 0.002). Compared with no changes or increases in urine cfDNA KRASG12/G13 copies during therapy, decreases in these measures were associated with longer median time to treatment failure (P = 0.03).Conclusions: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA had good concordance with testing of archival tumor tissue. Changes in mutated urine cfDNA were associated with time to treatment failure.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
cell, free DNA, DNA, unclassified drug, cell free nucleic acid, KRAS protein, human, protein p21, tumor marker
Elenco autori:
Fujii, Takeo; Barzi, Afsaneh; Sartore-bianchi, Andrea; Cassingena, Andrea; Siravegna, Giulia; Karp, Daniel; Piha-paul, Sarina; Subbiah, Vivek; Tsimberidou, Apostolia M; Huang, Helen; Veronese, Sillvio; DI NICOLANTONIO, Federica; Pingle, Sandeep C; Vibat, Cecile Rose T; Hancock, Saege; Berz, David; Melnikova, Vladislava O; Erlander, Mark G; Luthra, Rajyalakshmi; Kopetz, Scott; Meric-bernstam, Funda; Siena, Salvatore; Lenz, Heinz-josef; Bardelli, Alberto; Janku, Filip
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