Early Drive Mutations of IDH Wild GBM

By analyzing 21 pairs of primary GBM and local recurrence of IDH wild type GBM, the German Cancer Research Center (DKFZ) Department of Systems Biology, and others found that most GBM caused tumors to occur through the acquisition and loss of specific chromosomes, and THAT TERT promoter mutations were a prerequisite for the rapid growth of GBMThe findings were published in Cancer Cell in April 2019- From the article chapter
(Ref: K?rber V, et alCancer Cell2019 Apr 15;35(4): 692-704.e12doi: 10.1016/j.ccell.2019.02.007Epub 2019 Mar 21glioblastoma (GBM) is the most common adult malignant brain tumorDue to the substantial immersion growth of GBM cells to the surrounding brain and the high heterogeneity of glioma, the 5-year survival rate of IDH wild GBM patients was only 6%By analyzing 21 pairs of primary GBM and local recurrence of IDH wild type GBM, the German Cancer Research Center (DKFZ) Department of Systems Biology, and others found that most GBM caused tumors to occur through the acquisition and loss of specific chromosomes, and THAT TERT promoter mutations were a prerequisite for the rapid growth of GBMThe findings were published in Cancer Cell in April 2019researchers used whole genome sequencing, DNA methylation analysis, transcriptome sequencing, and targeted sequencing to detect primary and first recurrence of IDH wild-type GBM expressionEach GBM subtype is determined by DNA methylationThe correlation between mesotype (MES) subtypes and tumor purity and immune cell immersion was observed before confirming subtype groupings and whole genome sequencing and transcription group levelsIt was found that 8 of GBM's 50 subtypes were MES subtypesAfter 90% of patients were treated, the subtype did not changein the coding regions of 28 genes, 13 non-coding RNA genes, and TERT promoters, the authors found that at least three tumor samples could detect driving mutationsAt least three of the 21 paired tumors were increased or lost, including: the entire chromosome 10 or q arm is missing, containing the PTEN gene seat; Through the absence of exon 2-7, 44% of EGFR amplification and EGFRvIII mutations occurred simultaneously, and in three samples, chromosomal translocation occurred near eGFR super-enhanced elementsauthors observed that 12% of primary and recurrent samples had a common mutation7% of the mutations are determined to be clones in primary tumors and subclones in recurrent tumorsThe subclonal structure of primary and recurrent tumor pairing samples was identified, and each sample could usually distinguish between 2 to 3 subclons with a size level of cloningOf the 21 paired samples, 15 tumor recurrences came from more than one clone of primary tumorsstudies found that chromosome 7 increased, chromosomal arm 9p/CDKN/B bureau-type lesions lost, and the system development tree in the common stem of 10/10q chromosome lossIn 21 tumor-paired samples, 20 clones had copy-number variations and at least one chromosome was acquired or lostIn contrast to copy number variation, most relapsed tumors are subclonon, with the exception of mutations in TP53, PTEN, EGFR, and TERT promotersthe whole genome sequencing data of the study showed that during tumor evolution, a series of nuclear proliferation-driven mutations occurred at an early stage, affecting the number of copy variants of CDKN/B, PTEN or EGFRTerT promoter mutations are found in almost all tumors with a high degree of subclonalityThe authors hypothesized that a large number of tumor cells died before the TERT promoter mutation, followed by a terT promoter mutation that reduced cell mortality by 6% to 26%in the study, the authors revealed the genetic diversity of primary and recurrent IDH wild glioblastomaThe different DNA methylation subgroups of all tumors reflect a common pathway for early tumor occurrence, some of which is achieved through the loss or addition of chromosomes to obtain a characteristically driven mutation; At present, the global glioma research is in-depth discussion of the occurrence-recurrence mutation model of glioma, the aim is to find effective treatment targets.