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- W4224063904 abstract "Abstract Background: Targeted therapy of glioma is unsatisfactory due to the variable heterogeneity of tumors. We tracked glioma genomic alterations in vivo to provide a boost to precision medicine. Methods: We collected tumor tissue samples from glioma patients (including recurrent tumors) and serially collected Tumor in situ fluid (TISF) after surgery. Glioma-derived DNA from these samples was sequencing by next-generation DNA sequencing. We longitudinally analysed the genomes of glioma patients in tumor and TISFs, and explored the relationship between characteristic alterations in glioma evolution and targeted therapies, key clinical treatment options, imaging, treatment response. Results: We validated the representativeness of TISF circulating tumor DNA (ctDNA) to the tumor genome, 100% (33/33) of the mutations detected in the recurrent tumors were detectable in the TISF samples. there was a significant correlation between recurrent tumors variant allele frequencies (VAFs) and the TISF ctDNA VAFs (R 2 = 0.9029, 0.9189). In addition, TISF ctDNA is associated with glioma progression and prognosis. The significant alterations observed after tumor progression were KIT (P = 0.0156), NF1 (P = 0.0078), TSC2 (P = 0.0313), FAT1 (P = 0.0313), SMO (P = 0.0313), RTK/RAS/PI3K pathway (P = 0.0028) and MMR gene (P = 0.0234). And we captured the glioma genomic landscape real-time in vivo and found a complete subclonal selection process of PDGFRA, CDKN2A and mismatch repair gene related mutations which were suggested to be actionable for targeted agents. We also identified the progressively increased number and proportion of temozolomide-related C>T/G>A transitions in glioma genome under temozolomide treatment. These key genetic alterations are associated with clinical progression confirmed on imaging, suggesting their driving role for tumor recurrence and the significance to precise therapy. Conclusions: Increased TISF ctDNA were associated with disease progression and prognosis. Serial ctDNA testing identified progression alterations. Longitudinal ctDNA evaluation could monitor tumour genomic evolutionary patterns and guide precision medicine." @default.
- W4224063904 created "2022-04-19" @default.
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- W4224063904 date "2022-04-18" @default.
- W4224063904 modified "2023-09-23" @default.
- W4224063904 title "Tracking Glioma Evolution in human brain for precision medicine by integrating real-time in vivo tumour genomes" @default.
- W4224063904 doi "https://doi.org/10.21203/rs.3.rs-1550999/v1" @default.
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