PMC6735656_01
Radiological assessments of tumor response and molecular profiling in ctDNA and tumor tissue.. Abbreviation: ctDNA, circulating tumor DNA.
OTT-12-7323-g0001.jpg
PMC6735656_01_OTT-12-7323-g0001.jpg
F0001
After 6 weeks of treatment, with the tumor size reduction, the VAF of MET mutation dropped to below the limit of detection and remained undetected in subsequent cycles at weeks 18, 24, 30 and even at time of progression (week 36) (Figure 1). Interestingly, MET amplification was not detected by NGS in tumor biopsy specimen at disease progression (Figures 1 and 2).
Copy number profile of tumor tissue. Left column: baseline; Right column: after 36 weeks at time of progression.. Notes: (A) Next-generation sequencing (NGS, left panels) copy number plots of the KRAS locus on chromosome 12 from savolitinib-naive and savolitinib-resistant tumors. Fluorescence in situ hybridization (FISH) for KRAS (red) and centromere 12 (CEN12, green) is shown for savolitinib-resistant tumor. (B) NGS copy number plots of EGFR/MET locus on chromosome 7 from savolitinib-naive and savolitinib-resistant tumors. FISH for EGFR (red) and centromere 7 (CEP7, green) is shown for savolitinib-resistant tumor. (C) NGS copy number plots of FGFR1 locus on chromosome 8 from savolitinib-naive and savolitinib-resistant tumors. FISH for FGFR1 (green) and centromere 8 (CEP8, red) is shown for savolitinib-resistant tumor.. Abbreviations: NGS, next-generation sequencing; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; FISH, fluorescence in situ hybridization; CEN12, centromere 12; FGFR, fibroblast growth factor receptor; CEP7, chromosome enumeration probe 7; CEP8, chromosome enumeration probe 8.
OTT-12-7323-g0002.jpg
PMC6735656_01_OTT-12-7323-g0002.jpg
F0002
In addition, moderate levels of gene copy numbers of EGFR (GCN =5.7), FGFR1 (GCN =5.8) and KRAS (GCN =4.5) were newly identified by NGS at disease progression and were further confirmed using fluorescence in situ hybridization technology (Figure 2). Interestingly, MET amplification was not detected by NGS in tumor biopsy specimen at disease progression (Figures 1 and 2).