AMED医薬品等規制調和・評価研究事業 「遺伝子パネル検査 …

1 1 AMED FoundationOne CDx OncoGuide NCC 2018 12 2019 6 companion diagnostics system: CDx comprehensive genomic profiling: CGP FoundationOne Liquid CDx 2021 3 2021 8 CDx CDx CD PMDA WG 25 12 26 CDx CGP CDx CDx 5 31 CGP

2 CGP CDx AMED (limit of detection: LOD) CGP CDx CGP CGP validation validation 2

3 Single or multiple nucleotide variant: SNV/MNV insertion/deletion: Ins/Del copy number variation: CNV Fusion CGP DNA PMDA SNV/MNV Ins/Del Horizon AcroMetrix 2019 5 31 Medical Device Innovation Consortium SRS Report.

4 Somatic Variant Reference Samples for NGS ( ) Horizon HD701 HD827 HD Tru-Q variant allele frequency VAF GC HD827 LOD VAF hit rate LOD hit rate hit rate VAF SNV

5 LOD LOD Ins/Del PCR NGS ( ) VAF 3 SNV/MNV multiple nucleotide variant , Ins/Del PMDA WG 90% Ins/Del (EGFR V769_D770insASV, EGFR E746 - A750 ) Ins/Del GC (GNA11 Q209L, AKT1 E17K ) pseudogene MNV DNA SNV/MNV Ins/Del RNA fusion fusion Medical Device Innovation Consortium FDA Sequencing and Quality Control (SEQC) VAF Jones W, et al.

6 A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency. Genome Biol. 2021;22:111 CGP LOD LOD VAF hit rate quality control PCR VAF CDx CGP CGP LOD CDx LOD Ins/Del CDx CDx

7 4 Ins/Del CDx CDx CNV Horizon HD753 MYC-N MET Droplet Digital PCR NIST Reference Material 8366 He HJ, et al. Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements. Clin Chem Lab Med. 2019;57:1142-1152 EGFR MET PCR NIST Reference Material 8366 6 PCR 6 PCR MET Hs746T NGS ( ) MET PCR PCR ERBB2 NIST Reference Material 2373 Lih CJ, et al.

8 Certified DNA Reference Materials to Compare HER2 Gene Amplification Measurements Using Next-Generation Sequencing Methods. J Mol Diagn. 2016;18:753-761 DNA PCR PCR CNV LOD hit rate VAF validate CNV ploidy ploidy CNV or

9 ATCC (American Type Culture Collection) CNV LOD DNA ATCC DNA ATCC QIAGEN PCR 5 PCR ATCC PCR PCR CNV DNA ATCC 2 PCR ERBB2 CDx CNV PCR FISH IHC FISH PCR PCR

10 ATCC euploidy IHC FISH heterogeneity CNV IHC FISH CNV SNV/MNV, Ins/Del CGP MET EGFR MYC-N ERBB2 LOD LOD hit rate Hs746T CDx CGP CGP LOD CDx CDx CGP LOD ERBB2 CDx IHC CNV CDx CDx CDx