/( ytiliytilibaborbaborytiliytilibaborbaborBMTseneGdeta tP0P0PP00uM0TP53KRASLRP1BFGFR1KEAP1MYCBARD1SMARCA4METFGF3NRG1PTPRDTFRCCDK4PIK3CAAREGFRERBB2ERCC2PTPRTSPTA1AKT2ARID2ATMBRAFBRCA2CARD11CDKN2AFGF19FLT1MDM2PRKDCZFHX3ALKARID1BCCND1FAT1FGF4LATS2MYCNNF1NFE2L2NTRK1PDGFRBPIK3C2GPREX2RETRICTORRPS6KB1SLX4SPENSTK11)bMMutated geneTP53KRASMYCCDK4METPIK3CAERBB2KEAP1CDKN2AEGFRFGF19FGFR1(A)(C)311.00.80.60.40.20.01.00.80.60.40.20.0Nonsense_MutationFrame_Shift_DelMissense_MutationFrame_Shift_Ins10200400600800100012001400Splice_SiteAmpMulti_HitComplex_Event20304050MutantWT(B)(D)1.00.80.60.40.20.01.00.80.60.40.20.0Median TMB (/Mb);9.4[2.4-30.6]200400600800100012001400200400600800100012001400TP53 + ERBB2 amp (p<0.005)PFS (days.)KEAP1 (p=0.191)PFS (days.)[%]673618131313111110101010Geneset [N= 5]WT [N= 56]MutantWT図2 TSO500により検出された遺伝子変異のheat mapMedian; 9.0 months[95%CI; 4.8-38.0]PFS (mo.)NFE2L2 (p=0.0684)PFS (days.)図3 PembrolizumabのPFSと変異との相関解析（A）PembrolizumabのPFS。（B）TP53変異＋ERBB2増幅を有する症例のPFS。（C）NFE2L2変異を有する症例のPFS。（D）KEAP1変異を有する症例のPFS。96
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