scholarly journals Morphological Spectrum and Survival Analysis of Diffuse Midline Glioma With H3K27M Mutation

Cureus ◽  
2021 ◽  
Author(s):  
Usman Hassan ◽  
Maliha Latif ◽  
Irfan Yousaf ◽  
Saad Bin Anees ◽  
Sajid Mushtaq ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Diffuse Midline Glioma ◽  
H3k27m Mutation

scholarly journals DIPG-78. REVERTANCE OF THE H3K27M MUTATION RESCUES CHROMATIN MARKS NECESSARY FOR ONCOGENESIS IN DIFFUSE MIDLINE GLIOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii302-iii302
Author(s):  
Cody Nesvick ◽  
Charles Day ◽  
Liang Zhang ◽  
Edward Hinchcliffe ◽  
David Daniels
Keyword(s):  
Critical Role ◽  
Aurora Kinase ◽  
Epigenetic Changes ◽  
Methionine Residue ◽  
H3 Phosphorylation ◽  
Diffuse Midline Glioma ◽  
H3k27m Mutation

Abstract Diffuse midline glioma (DMG) is a lethal brain tumor that typically occurs in children. Numerous studies have demonstrated the central role of the H3K27M mutation and secondary loss of H3K27 trimethylation (H3K27me3) in DMG tumorigenesis. Understanding how the H3K27M mutation alters the epigenetic landscape of the cell is necessary for revealing molecular targets that are critical to tumorigenesis. To investigate the epigenetic effects of H3K27M mutation in DMG, we developed revertant DMG cell lines with the mutant methionine residue reverted to wildtype (i.e., M27K). Revertant cells were analyzed for epigenetic changes and phenotypic differences in vitro and in vivo. H3M27K DMG cells grew in culture but displayed diminished proliferative capacity. H3M27K cells demonstrated total loss of H3K27M expression and restored trimethylation of H3K27 and H3K4. Furthermore, consistent with the hypothesis that the H3K27M mutation impacts H3 phosphorylation via expression of Aurora Kinase during mitosis, H3M27K cells demonstrated reduced expression of both Aurora Kinase A and phosphorylation of H3 serine residues 10 and 28. In line with the critical role of H3S10 phosphorylation in chromatin segregation, H3M27K cells also demonstrated restored chromosome segregation compared to H3K27M cells. In vivo data will be discussed. Revertance of the H3K27M mutation reduces tumorigenesis in DMG tumors. Isogenic H3M27K cells display reversal of key epigenetic changes associated with oncogenesis in DMG. The revertant H3M27K DMG model is a useful tool to investigate the downstream epigenetic reprogramming specific to H3K27M mutation in these tumors.

Liquid biopsy for diffuse intrinsic pontine glioma: an update

2019 ◽  
Vol 24 (5) ◽  
pp. 593-600 ◽  
Author(s):  
Victor M. Lu ◽  
Erica A. Power ◽  
Liang Zhang ◽  
David J. Daniels
Keyword(s):  
Liquid Biopsy ◽  
Surgical Intervention ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Biological Information ◽  
Attractive Alternative ◽  
Pontine Glioma ◽  
Surgical Biopsy ◽  
Biological Sampling ◽  
Diffuse Midline Glioma ◽  
H3k27m Mutation

Diffuse intrinsic pontine glioma (DIPG), otherwise known as diffuse midline glioma with H3K27M mutation, is a devastating brainstem glioma without a cure. Efforts are currently underway to better optimize molecular diagnoses through biological sampling, which today remains largely limited to surgical biopsy sampling. Surgical intervention is not without its risks, and therefore a preference remains for a less invasive modality that can provide biological information about the tumor. There is emerging evidence to suggest that a liquid biopsy, targeting biofluids such as CSF and blood plasma, presents an attractive alternative for brain tumors in general. In this update, the authors provide a summary of the progress made to date regarding the use of liquid biopsy to diagnose and monitor DIPG, and they also propose future development and applications of this technique moving forward, given its unique histone biology.

scholarly journals Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

2019 ◽  
Vol 12 (10) ◽  
pp. e231424 ◽  
Author(s):  
Kelsey Peters ◽  
Drew Pratt ◽  
Carl Koschmann ◽  
Denise Leung
Keyword(s):  
Spinal Cord ◽  
Cervical Spine ◽  
Histone Deacetylase Inhibitor ◽  
Recurrent Disease ◽  
Prolonged Survival ◽  
Adjuvant Temozolomide ◽  
Deacetylase Inhibitor ◽  
Adult Spinal Cord ◽  
Diffuse Midline Glioma ◽  
H3k27m Mutation

We report a case of prolonged survival in a patient with known cervical intramedullary H3K27M-mutant diffuse midline glioma. A 39-year-old man presented for evaluation with several months of progressive upper extremity pain and weakness. MRI of the cervical spine revealed an intramedullary ring-enhancing lesion centred at C3-C4. Following subtotal surgical resection, a diagnosis of glioblastoma (GBM) was confirmed. Subsequent testing at a later date revealed an H3K27M mutation. He was initially treated with radiation and concomitant and adjuvant temozolomide. He had multiply recurrent disease and was treated with various regimens, including the histone deacetylase inhibitor valproic acid. The patient passed away 31 months (~2.5 years) after diagnosis. Our case is one of few reported adult spinal cord GBMs possessing the H3K27M mutation, and one with the longest reported overall survival in the literature to date.

scholarly journals DIPG-17. BIOPSY-PROVEN DIFFUSE MIDLINE GLIOMA IN ADOLESCENTS AND YOUNG ADULTS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii290-iii290
Author(s):  
Shota Tanaka ◽  
Shunsaku Takayanagi ◽  
Yuki Shinya ◽  
Mariko Kawashima ◽  
Masahiro Shin ◽  
...  
Keyword(s):  
Young Adults ◽  
Idh1 Mutation ◽  
Adolescents And Young Adults ◽  
Molecular Profile ◽  
Diffuse Astrocytoma ◽  
Genetic Analyses ◽  
K27m Mutation ◽  
Histological Confirmation ◽  
Diffuse Midline Glioma ◽  
H3k27m Mutation

Abstract INTRODUCTION Diffuse midline glioma (DMG) mostly affects young children. The newly-introduced disease entity DMG, H3K27M-mutant uniformly portends poor prognosis, and therefore that in the pons is usually treated based upon radiological diagnosis without histological confirmation. DMG is rarer in adolescents and young adults (AYA), and remains poorly characterized. In this study, we sought to investigate the clinical, pathological, and molecular profiles of DMG in AYA generation. METHODS Patients of age between 16 and 39 undergoing biopsy at the University of Tokyo Hospital between 2003 and 2019 were included in the study. Clinical data and images were retrospectively reviewed. Genetic analyses were performed in cases with abundant tissues. RESULTS Ten patients included 8 brainstem and 2 thalamic DMG. The median age was 25 years (range, 19–38). Pathological diagnosis was DMG, H3K27M-mutant in 3 patients, glioblastoma, IDH-mutant in 1, anaplastic astrocytoma, IDH-wildtype in 4, diffuse astrocytoma, IDH-mutant in 1, and diffuse astrocytoma, IDH-wildtype in 1. Genetic analyses detected H3F3A-K27M mutation in 2, HIST1H3B-K27M mutation in 1, IDH1-R132H mutation in 1, and IDH1-R132S mutation in 1. With a median follow-up of 23 months (range, 2–61), only 3 patients died 29–61 months after diagnosis, and the remaining 7 patients survived for 2–59 months. Neither IDH1 mutation nor H3K27M mutation was associated with survival in this series. CONCLUSION Survival of AYA patients with DMG was seemingly variable with some long survivors. H3K27M mutation was present in a subset of patients. A further study is warranted to correlate molecular profile with clinical pictures including patient survival.

Risk for psychotherapy drop-out in survival analysis: The influence of general change mechanisms and symptom severity.

2020 ◽  
Vol 67 (6) ◽  
pp. 712-722
Author(s):  
Sebastian Gmeinwieser ◽  
Kai Sebastian Schneider ◽  
Maximilian Bardo ◽  
Timo Brockmeyer ◽  
York Hagmayer
Keyword(s):  
Survival Analysis ◽  
Symptom Severity ◽  
Drop Out ◽  
General Change ◽  
Change Mechanisms

Five-year Survival Analysis of a Cohort of Hepatocellular Carcinoma Patients Who Treated at the National Cancer Center, Korea

2007 ◽  
Vol 13 (4) ◽  
pp. 530 ◽  
Author(s):  
Kyung Woo Park ◽  
Joong-Won Park ◽  
Tae Hyun Kim ◽  
Jun Il Choi ◽  
Seong Hoon Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Cancer Center

A Study on insolvency factors of Housing Sale Guarantee Using Survival Analysis

2017 ◽  
Vol 25 (4) ◽  
pp. 51-72
Author(s):  
Hyuck-Shin Kwon ◽  
◽  
Doo-Won Bang ◽  
Myeong-Hyeon Kim ◽  
◽  
...  
Keyword(s):  
Survival Analysis
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