asco@alo33:161987 JSONTXT

Background: Current methods to extract DNA from plasma are limited by the harvesting of small quantities of poor quality DNA. Circulogene Theranostics has developed a CLIA-certified proprietary method enabling the recovery of necrosis and apoptosis-associated, cell-free cf -DNA, ith a high-yield 300 ngml of sequencing quality DNA from a drop of plasma. We report cfDNA sequencing data from mCRPC patients pts using this novel methodology. Methods: Pts ith mCRPC underent prospective blood collection at UAB. Tenty microliters of plasma collected in a microtainer EDTA tube as used for the harvesting of cfDNA. An automated orkstation that can process up to 96 samples facilitates consistent and reliable studies ith a turnaround time of 7-10 days. DNA is subjected to targeted ultra-deep 2,000X 15,000X Next Generation Sequencing NGS on the Ion Torrent platform to detect approximately 3000 hotspot mutations in 50 potentially actionable genes. Germline and unconfirmedsilent somatic mutations and mutations ith allele frequency lt 1 percent are filtered out based on dbSNP, 1000 genomes and COSMIC. Results: Plasma samples ere available from 27 patients ith mCRPC. A median of 840 ng range 280-1640 of DNA as recovered from 20 xB5;L of plasma per patient. The most common mutation at baseline as in the P53 gene, seen in 7 pts 25.9 percent , folloed by KIT in 3 pts 11.1 percent and VEGFR2 in 2 pts 7.4 percent . Mutations seen in 1 patient each 3.7 percent ere ALK, CTNNB1, EGFR, ERBB4, FGFR3, HNF1A, HRAS, IDH1, JAK3, KRAS, NOTCH1, PIK3CA, PTEN, PTPN11, RET, SMAD4 and VHL. Activating mutations ere seen in ALK, HRAS, IDH1, JAK3 and VEGFR2, and inactivating mutations ere seen in P53, PTEN and VHL. The dataset is expanding and results ill be updated from a larger number of pts. Conclusions: Multiple potentially actionable therapeutic targets ere identified by cfDNA sequencing of pts ith mCRPC. This novel methodology facilitates the yield of large quantities of high fidelity DNA from minimal quantities of plasma, and appears promising to serially and non-invasively profile tumor DNA and inform on clonal evolution in a time and cost-efficient manner.,J Clin Oncol 34, 2016 suppl; abstr e16579 ,Publication Only Genitourinary Prostate Cancer