부산대학교 도서관

Background The necessary condition for the application of precision oncology approach into the routine is a detailed molecular characterization of the tumour. In our study, we explored clinical applicability of both whole exome sequencing (WES) and FoundationOne Heme (F1Heme) panel (Foundation Medicine, Inc. MA, USA) as comprehensive genomic profiling tools in a cohort of 35 children with difficult-to-treat solid tumours. Methods WES (both somatic and germline) in children with high-risk solid tumours was performed using TruSeq DNA Exome Kit, NextSeq 500/550 Mid Output Kit and NextSeq 500 sequencing device (all Illumina, CA, USA). Sequencing data were processed by an established pipeline. Tumour mutational burden (TMB) was calculated as a number of coding and splice-site nonsynonymous SNVs per megabase. FFPE samples from 35 patients previously examined by WES were independently examined also by F1Heme. Finally, we compared findings provided by WES and F1Heme with focus on clinically relevant information. Results Clinically relevant SNVs were identified using both WES and F1Heme in 13 patients (37%). Among mutated genes were NRAS (5 patients), FGFR1 (2 patients), CTNNB1 (2 patients), PTPN11 (2 patients) BRAF (1 patient), IDH2 (1 patient) and HIST1H3B (1 patient). Nine patients carried also mutation in TP53. There was a significant correlation between TMB values obtained by WES and F1Heme (R2=0.998, P < 0.001), whereas in 2 patients TMB was higher than 10 mut/Mb. F1Heme also reported gene rearrangements and amplifications. Conclusions We found 100% match in detection of SNVs using both WES and F1Heme. TMBs obtained from WES and F1Heme were correlated with high statistical significance. Our data suggest that the molecular diagnostics based both on WES and F1Heme present valuable tools for individualized treatment planning for detecting SNVs in paediatric oncology. WES needs to be complemented by other profiling tools to detect other types of genomic alterations such as gene rearrangements or amplification. Legal entity responsible for the study The authors. Funding Roche supplies FoundationOne Heme with tests and by the Czech Ministry of Health, grant no 16-33209A. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]