6533b833fe1ef96bd129c237
RESEARCH PRODUCT
Validating comprehensive next-generation sequencing results for precision oncology : The NCT/DKTK molecularly aided stratification for tumor eradication research experience
Daniela RichterDaniela RichterSebastian BauerIvo BuchhalterCristiano OliveiraCristiano OliveiraMelanie BoerriesAmelie LierFrederick KlauschenStephan WolfEsther HerpelEsther HerpelPeter HorakAnna-lena VolckmarPeter LichterThomas KindlerChristof Von KalleStefan FrohlingStefan FrohlingKlaus Schulze-osthoffOlaf NeumannSebastian UhrigSebastian UhrigJonas LeichsenringHanno GlimmHanno GlimmPeter SchirmacherPeter SchirmacherAlbrecht StenzingerAlbrecht StenzingerMartina FröhlichMario LampingPhilipp J. JostBenedikt BrorsStephan SingerGunnar FolprechtHans-georg KoppKatrin PfützeNikolas Von BubnoffJ. BudcziesBarbara HutterWilko WeichertChristoph HeiningChristoph HeiningJohanna FalkenhorstKlaus H. MetzelerDamian T. RiekeRoland PenzelSimon KreutzfeldtSimon KreutzfeldtMartina KirchnerVolker EndrisEvelin SchröckChristian Brandtssubject
0301 basic medicineCancer Researchmedicine.medical_specialtyStandardizationComputer sciencePersonalized treatmentMedizinGenomicsDNA sequencing03 medical and health sciences030104 developmental biology0302 clinical medicineWorkflowOncologyPrecision oncology030220 oncology & carcinogenesismedicineMedical physicsCancer biologydescription
Purpose Rapidly evolving genomics technologies, in particular comprehensive next-generation sequencing (NGS), have led to exponential growth in the understanding of cancer biology, shifting oncology toward personalized treatment strategies. However, comprehensive NGS approaches, such as whole-exome sequencing, have limitations that are related to the technology itself as well as to the input source. Hence, clinical implementation of comprehensive NGS in a quality-controlled diagnostic workflow requires both the standardization of sequencing procedures and continuous validation of sequencing results by orthogonal methods in an ongoing program to enable the determination of key test parameters and continuous improvement of NGS and bioinformatics pipelines. Patients and Methods We present validation data on 220 patients who were enrolled between 2013 and 2016 in a multi-institutional, genomics-guided precision oncology program (Molecularly Aided Stratification for Tumor Eradication Research) of the National Center for Tumor Diseases Heidelberg and the German Cancer Consortium. Results More than 90% of clinically actionable genomic alterations identified by combined whole-exome sequencing and transcriptome sequencing were successfully validated, with varying frequencies of discordant results across different types of alterations (fusions, 3.7%; single-nucleotide variants, 2.6%; amplifications, 1.1%; overexpression, 0.9%; deletions, 0.6%). The implementation of new computational methods for NGS data analysis led to a substantial improvement of gene fusion calling over time. Conclusion Collectively, these data demonstrate the value of a rigorous validation program that partners with comprehensive NGS to successfully implement and continuously improve cancer precision medicine in a clinical setting.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-02-09 |