Impact of DNA integrity on the success rate of tissue-based next-generation sequencing: Lessons from nationwide cancer genome screening project SCRUM-Japan GI-SCREEN

SCRUM-Japan GI-SCREEN Pathology Group

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1 Citation (Scopus)

Abstract

In the nationwide cancer genome screening project SCRUM-Japan GI-SCREEN, 2590 archival formalin-fixed paraffin-embedded (FFPE) tumor tissues from 19 institutions were analyzed with two tissue-based next-generation sequencing (NGS) panels at the Clinical Laboratory Improvement Amendments (CLIA)-certified College of American Pathologists (CAP)-accredited central laboratory. The Oncomine Cancer Research Panel (OCP; 143 genes) succeeded in producing validated results for only 68.3% of the samples (%OCP-success). CE-IVD (25 genes) succeeded in 45.9% of the OCP-failed samples, leading to an overall NGS success (%combined-success) rate as high as 82.9%. Among 2573 samples, the DNA-integrity (ΔCt)-high (ΔCt < 4.4, n = 1253) samples showed significantly higher %OCP- and %combined-success rates (90.2% and 97.4%, respectively) than the DNA-integrity-intermediate (4.4 < ΔCt < 6.3, n = 911; 68.9% and 88.7%) and DNA-integrity-low ones (ΔCt > 6.3 or polymerase chain reaction-failed, n = 409; 5.6% and 24.7%). Other factors associated with NGS success included the FFPE-sample storage period (<4 years), the specimen type (surgical) and the primary tumor site (colorectal). Multivariable analysis revealed DNA integrity as the factor with the strongest independent association with NGS success, although it was suggested that other institution-specific factors contribute to the discordance of inter-institutional NGS success rates. Our results emphasize the importance of DNA quality in FFPE samples for NGS tests and the impact of DNA integrity on quality monitoring of pathology specimens for achieving successful NGS.

Original languageEnglish
Pages (from-to)932-942
Number of pages11
JournalPathology International
Volume70
Issue number12
DOIs
Publication statusPublished - Dec 2020

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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