Prospects for the application of clinical sequencing of adult glioma

Siyuan Zheng of the Neurotumor Department at the University of Texas Anderson Cancer Center used the T200 gene panel of the Anderson Cancer Center to conduct a forward-looking cohort study of 237 glioma specimens to assess the prognosis of glioma patients and the role of the gene panel in determining the prognosis of glioma patients and selecting effective treatment skewedsThe results were published in Molecular Cancer Therapeutics in May 2019- Excerpted from the article(Ref: Zheng S, et alMolMol Cancer Ther2019 May;18 (5): 991-1000doi: 10.1158/1535-7163.MCT-18-1122The Epub 2019 Mar 29Cancer Genome Atlas (TCGA) project has detected high-frequency mutation genes for gliomas, including EGFR, TP53, and IDH1, through genome-wide high-throughput sequencingWhole genome sequencing is time-consuming, laborious, and costly, so selecting specific genes for targeted sequencing may be a more clinically appropriate method of sequencingBoth the Basic Medical Gene Panel (Panel) and the IMPACT panel at memorial Kettering Cancer Center are both fda-approved for clinical high-throughput targeted genetic testingSiyuan Zheng of the Neurotumor Department at the University of Texas Anderson Cancer Center used the T200 gene panel of the Anderson Cancer Center to conduct a forward-looking cohort study of 237 glioma specimens to assess the prognosis of glioma patients and the role of the gene panel in determining the prognosis of glioma patients and selecting effective treatment skewedsThe results were published in Molecular Cancer Therapeutics in May 2019the authors used homemade gene panels to conduct forward-looking ultra-deep targeted sequencing of 237 glioma specimens in 234 patientsSequencing samples are tumor specimens and peripheral white blood cells buried in paraffinGene sequencing panel T200 and T200.1 contain 4874 and 5003 exons, respectively, including high-frequency mutations such as TP53, IDH1, common in gliomas The authors detected a total of 2,485 cell mutations, including single nucleotide substitution and small insertion deficiencies Anti-cancer genes such as PTEN, RB1, and ATRX all have inactivated mutations caused by insertion deficiencies and discontinuation of transcription (Figure 1) Figure 1 234 clinical sequencing results of gliomas study showed that TP53 was the most mutated gene, followed by IDH1, EGFR and PTEN EGFR mutations were detected in 23% of low-grade gliomas (LGGs), significantly higher than 6% of TCGA This difference may be due to different patient composition and sequencing depth When the mutation allele fraction (VAF) of EGFR was detected, it was found that the VAF of less protogliolitosand and astrocytosma was significantly lower than glioblastoma, suggesting that the EGFR mutation may be present in a small number of glioma cells (Figure 2) Figure 2 Mutations between different gliomas in 83% LGG and 77% secondary GBM, the frequency of IDH hotspot mutations was higher than 9% of primary and relapsed GBM Multivariate analysis of age, histology, and tumor levels confirmed the value of the idh mutation prediction prognosis The optimization prediction results were 64% sensitive and 100% specific, compared with the fluorescent insitilate hybridization (FISH) results of 50 tumors, using sequencing data finally, the authors found high-frequency mutations in 12 glioma samples In the 12 glioma samples, 95% of the mutations in 7 points were CT mutations The authors note that high-frequency mutations in recurrent LGG and secondary GBM typically differ years from initial diagnosis to tumor sequencing, with intervals greater than single relapsed GBM cases After evaluating the relationship between high-frequency mutations and prognosis, the authors note that the prognosis of patients is consistent with previous retrospective analysis Therefore, the results show that ultra-deep target sequencing is expected to obtain the results of previous whole genome sequencing, with clinical application value.