Abstract 3146: Circulating tumor DNA assay performance for detection and monitoring of KRAS mutations in urine from patients with advanced cancers

Autor: Vivek Subbiah, Kiran Madwani, Mark G. Erlander, David S. Hong, Scott Kopetz, Sarina Anne Piha-Paul, Saege Hancock, Filip Janku, Aung Naing, Helen J. Huang, Daniel D. Karp, Rajyalakshmi Luthra, Cecile Rose T. Vibat, Apostolia Maria Tsimberidou, Bryan K. Kee, Vlada Melnikova, Debra L. Andrews, Siquing Fu, Takeo Fujii, Funda Meric-Bernstam
Rok vydání: 2016
Předmět:
Zdroj: Cancer Research. 76:3146-3146
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2016-3146
Popis: Introduction: Non-invasive urinary ctDNA-based liquid biopsy approach can be used to detect and track cancer driver mutations for rapid diagnosis and disease monitoring. Using highly sensitivity ctDNA mutation detection platform, we examined the detection of KRAS G12/13 mutations in urine obtained from advanced cancer patients, assessed urine sample requirements, and compared the results with matched tumor tissue in patients with advanced cancers. Methods: 41 patients with advanced solid cancer with KRAS mutations on archival tumor from CLIA laboratory testing were prospectively enrolled with informed consent (colorectal cancer, n = 29; non-small cell lung cancer, n = 6; pancreatic cancer, n = 2; ovarian cancer, n = 2; other, n = 2). Urine was collected before and during experimental therapies. Urinary DNA was isolated using a method that enriches for highly fragmented, systemically derived cell-free DNA. KRAS G12/13 analysis was performed using mutation enrichment PCR coupled with next generation sequencing (MiSeq). Analytical sensitivity of the KRAS G12/13 assay is 0.006% mutant alleles in the background of 60 ng wild-type (wt) DNA and 0.002% mutant alleles in 360 ng wt DNA. Clinical data was collected retrospectively from the electronic medical record. Results: For 41 patients enrolled on a study, urine volumes in pretreatment samples ranged from 13 to 120 mL (median, 55 mL). Urinary DNA yields were 151 to 23059 ng (median, 1039 ng). Using tissue as the reference, the positive percent agreement (PPA) between urine and tumor KRAS G12/13 test results was 54% (22/41) for urine samples with all volumes (13-120 mL) and any DNA input amount (2-360 ng) and 92% (12/13) for urine samples with volumes ≥50 mL and DNA input amount ≥60 ng. For metastatic CRC patient cohort, the PPA between urine and tumor KRAS G12/13 test result was 60% (18/30) for urine samples with all volumes and any DNA input amount (20-120 mL, 2-360 ng) and 100% (10/10) for urine samples with volumes ≥50 mL and DNA input amount ≥60 ng. Feasibility of longitudinal monitoring KRAS G12/13 mutational burden in urine of patients treated with experimental therapies was demonstrated. Conclusion: KRAS G12/13 mutational status can be assess in urinary DNA with highest PPA amongst patients with urine volume ≥50 mL and DNA input amount ≥60 ng (92%). KRAS mutation detection from urine should be considered as a viable approach, particularly when tumor tissue is not available. Citation Format: Takeo Fujii, Cecile Rose T. Vibat, Daniel D. Karp, Sarina A. Piha-Paul, Vivek Subbiah, Apostolia M. Tsimberidou, Siquing Fu, David S. Hong, Helen J. Huang, Kiran Madwani, Debra L. Andrews, Saege Hancock, Aung Naing, Rajyalakshmi Luthra, Bryan K. Kee, Scott Kopetz, Mark G. Erlander, Vlada Melnikova, Funda Meric-Bernstam, Filip Janku. Circulating tumor DNA assay performance for detection and monitoring of KRAS mutations in urine from patients with advanced cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3146.
Databáze: OpenAIRE
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