Analysis of prognostic factors of diffuse midline glioma.

Diffuse mid-line glioma in children is a highly malignant brain tumor with a medium survival of 9-12 months.
because of the special location, surgery is very difficult, chemotherapy and other clinical trials have not made a breakthrough, so radiotherapy is still the basic treatment, but radiotherapy also only extended the survival of 3-4 months.
the prognosis of H3K27M gliomas in the diffuse mesothelioma, and there were no analysis results of molecular characteristics.
Florence Renaud of the Centre for Neuroscience and Oncology at the University Hospital of Lille in France analyzed the molecular characteristics of diffuse midline gliomas and potential prognostic markers, the results of which were published online in August 2019 in Brain Pathology.
The study reviewed and analyzed 49 children with diffuse midline glioma who were treated from January 2001 to March 2017.
the relationship between molecular characteristics and total survival is assessed by extracting tumor tissue DNA and RNA, conducting next-generation sequencing, comparing gene hybridization sequences, detecting KIAA1549-BRAF fusion, and immunoglobation analysis.
49 patients, 28 were male (57.1%) and 21 were female (42.9%);
9.4 months of the medium total lifetime (OS).
33 cases (67.3%) were located entirely in the brain, 11 cases (22.5%) occurred in the pasum, tricephalus, brain, spinal cord and pineal glycergy, and 5 cases (10.2%) were present in both the brain and the cerum.
15 cases (30.6%) were WHO IV.grade, 24 cases (49.0%) WHO III.class, and 10 cases (20.4%) WHO II. level.
9 cases (20.5%) without histone mutations (histone mutations, K27M).
28 cases (63.6%) of H3F3AK27M mutations, 7 cases (15.9%) of HIST1H3BK27M mutations, no H3F3B and HIS1H3C mutations were found.
study, the authors focused on the analysis of 35 cases (79.5%) of diffuse midline gliomas with H3F3A or HIST1H3B mutations.
In this subgroup, the median age of the children was 9 years (3-22 years) and the median overall survival was 7.9 months;
4 cases (11.4%) were found in both the brain and the pasum.
, 12 cases (34.3%) were diffuse IV.grade gliomas, 18 cases (51.4%) III.grade gliomas, and 5 cases (14.3%) II.grade gliomas.
20 cases (57.1%) of TP53 mutations and 2 cases (5.7%) of PPM1D mutations.
5 cases (14.3%) PIK3CA or PIK3R1 mutations and 4 cases (11.8%) ACVR1 mutations.
2 cases (5.7%) BRAF (V600E) occurred at the same time as the H3F3A K27M mutation.
all tumors retained the expression of INI1 and BRG1, and all histoprotein-mutated gliomas showed the absence of triple methylation of H3K27me3 in immunologicization.
most common chromosomal changes were 1q (44.1%), -5q (29.4%), -10q (44.1%), and -11q (26.4%) 5 per cent, -13 (41.2 per cent), -14 (52.9 per cent), -16q (35.3 per cent) and -17p (26.5 per cent).
complex changes in the structure of the chromosomes in 25 patients (70.6%).
addition, all tumors that lost 17p, including the TP53 gene base, were TP53 mutants.
ACVR1 mutation was significantly associated with the HIST1H3B mutation (57.1%:0%, P=0.001), while the p53 path change was significantly associated with the H3F3A mutation (75%:28.6%, P=0.033).
analysis of patients with diffuse mid-line glioma H3K27M mutations found that in patients with H3K27M mutations, PDGFRA amplification (P=0.010), 17p deficiency (P=0.008) and complex chromosome structures (P=0.044) were significantly associated with shorter total survival (Figure 1).
tumor location (P=0.879), EGFR over-expression (P=0.782), ACVR1 mutation (P=0.689), TP53 mutation (P=0.098), etc. were not significantly related to the overall lifetime.
compared with patients with THEHST1H3B mutation, the middle age of children with H3F3A mutation was 11 years (4-22 years), with a medium overall survival of 7.9 months, while the medium age of children with HIS1H3B mutation was 5 years (3-13 years) and the average survival period was 12.1 months.
9 cases of histoprotein wild subgroups, the middle age of the children was 11 years (1-19 years) and the average survival period was 27.3 months.
2 cases (22.2%) were diffuse IV.grade gliomas, 5 cases (55.6%) were III.grade gliomas, and 2 cases (22.2%) were Class II. gliomas.
5 cases (55.6%) of H3K27me3 were lost, of which 3 were ACVR1 mutations and 2 cases were TP53 mutations, and the median overall survival of these 5 cases was 13.2 months.
the chromosomes of histogeneic wild tumors changed less than those of H3K27M mutant tumors.
Figure 1. The overall lifetime of the H3K27M mutant subset is the main prognosmation indicator.
A.H3K27M mutation with or without 17p loss, B.H3K27M mutation with or without PDGFRA amplification, C.H3K27M mutation with or without complex chromosomal structure changes.
conclusions, there are three prognostic markers for diffuse midline H3K27M mutant gliomas: PDGFRA amplification, 17p loss, and complex chromosomal structures.
also have great heterogeneity in the H3K27M mutant glioma.
these prognostic markers can be used as intervention targets to improve patient prognostics.
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