LBA02-10 ACCURACY OF A SIMPLIFIED SEQUENCING AND BIOINFORMATICS PLATFORM ON GENETIC VARIANT DETECTION IN PROSTATE CANCER PATIENTS

Abstract

You have accessJournal of UrologyCME1 Apr 2023LBA02-10 ACCURACY OF A SIMPLIFIED SEQUENCING AND BIOINFORMATICS PLATFORM ON GENETIC VARIANT DETECTION IN PROSTATE CANCER PATIENTS Deepak Kapoor, Jonathan Anderson, and Ann Anderson Deepak KapoorDeepak Kapoor More articles by this author , Jonathan AndersonJonathan Anderson More articles by this author , and Ann AndersonAnn Anderson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003361.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Consensus guidelines suggest that genetic testing is clinically indicated for prostate cancer (PCa) patients who meet certain family history, stage and histopathological grade criteria. Current next generation sequencing (NGS) diagnostics rely on capital and maintenance intensive sequencers and require highly trained technical personnel to operate. This may restrict availability of testing where specimen transport or access to personnel/capital is limited. We sought to compare a simpler sequencer coupled with a bioinformatics platform which requires minimal maintenance and capital cost with traditional NGS equipment. METHODS: We compared results in detection of 10 genes recommended by NCCN PCa guidelines (ATM, BRCA1, BRCA2, CHEK2, MLH1, MSH2, MSH6, PALB2, PSM2, and HOXB13) between the Oxford Nanopore Technologies MinION to the Illumina NextSeq sequencer. All samples were sequenced in a depth greater than 50x. Bioinformatics for the Illumina sequencer was Illumina’s TruSight™ Hereditary Cancer panel. As the MinION reads long DNA fragments, and cancer diagnostics is focused on short exon sequencing, we used the CorrSeq Dx™ by Foresee Genomics to create long DNA molecules consisting of several tandem repeats of short DNA fragments separated by sequences recognized by the automated bioinformatics software. Statistical analysis was performed using Cohen’s kappa test. This IRB-exempt study was conducted in accordance with the Declaration of Helsinki. RESULTS: We detected using 380 variants in 13 patients on the Illumina platform and 379 (3 false negatives, 2 false positives) variants on the same patients using the MinION sequencer with CorrSeq Dx assay. The positive predictive value and sensitivity for the simplified platform was 99.5% (375/(375+2)) and 99.2% (375/(375+3)), respectively. The demonstrated accuracy of the simplified process was 99.9% (Cohen's kappa >0.99). CONCLUSIONS: Our data suggests that this application could allow smaller clinical laboratories which are currently outsourcing their NGS diagnostics to perform genetic testing in-house. Use of a simpler process for NGS testing could improve access to guideline-based care in remote and economically disadvantaged areas, resulting in better treatment outcomes as well as increased global healthcare equity. Further testing of this technology is warranted to further assess its impact on patient care. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1190 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Deepak Kapoor More articles by this author Jonathan Anderson More articles by this author Ann Anderson More articles by this author Expand All Advertisement PDF downloadLoading ...