scholarly journals In diffuse intrinsic pontine gliomas, non-coding RNA expression is significantly varied dependent on overall survival

2021 ◽  
Author(s):  
Henley Castillo ◽  
Kenzie Mellor ◽  
Amelia-Mae Marks ◽  
Willard L
Keyword(s):  
Overall Survival ◽  
Brain Cancer ◽  
Transcriptional Activity ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Rna Expression ◽  
Pontine Glioma ◽  
Non Coding Rna ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
New Treatments ◽  
Pediatric Brain

Abstract Diffuse intrinsic pontine glioma is a kind of pediatric brain cancer that kills 99 percent of patients within five years and for which there are no conventional chemotherapies. It is crucial for new treatments to comprehend the cancer's transcriptional activity. Using a published dataset, we compared the transcriptomes of tumors from patients who lived longer or less than six months. Among the genes whose expression changed most, we observed that numerous microRNAs and snoRNAs were present. The publication's findings are the first evidence of variable levels of non-coding RNA expression in diffuse intrinsic pontine glioma.

scholarly journals In diffuse intrinsic pontine gliomas, non-coding RNA expression is significantly varied dependent on overall survival

2021 ◽  
Author(s):  
Rucha ◽  
Vijay S
Keyword(s):  
Overall Survival ◽  
Brain Cancer ◽  
Transcriptional Activity ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Rna Expression ◽  
Pontine Glioma ◽  
Non Coding Rna ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
New Treatments ◽  
Pediatric Brain

Abstract Diffuse intrinsic pontine glioma is a kind of pediatric brain cancer that kills 99 percent of patients within five years and for which there are no conventional chemotherapies. It is crucial for new treatments to comprehend the cancer's transcriptional activity. Using a published dataset, we compared the transcriptomes of tumors from patients who lived longer or less than six months. Among the genes whose expression changed most, we observed that numerous microRNAs and snoRNAs were present. The publication's findings are the first evidence of variable levels of non-coding RNA expression in diffuse intrinsic pontine glioma.

scholarly journals Non-coding RNA are differentially expressed in diffuse intrinsic pontine gliomas based on overall survival.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Brain Cancer ◽  
Expression Profiling ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Novel Therapies ◽  
Pontine Glioma ◽  
Non Coding Rna ◽  
Differential Gene ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
Pediatric Brain

Diffuse intrinsic pontine glioma is a pediatric brain cancer; 99% of patients diagnosed with this disease will expire within 5 years (1) and there are no standard chemotherapies available for it (2). Understanding the transcriptional behavior of this cancer is critical for the development of novel therapies. We performed global differential gene expression profiling of tumors from patients with DIPG by comparing the transcriptomes of tumors from those who survived greater or less than six months using a published dataset (3). We found that multiple microRNAs and snoRNAs were among the genes whose expression was most different between those who survived greater or less than six months. This is the first report of outcome-associated differential expression of non-coding RNA in diffuse intrinsic pontine glioma.

scholarly journals Genes encoding histone proteins are differentially expressed between men and women with diffuse intrinsic pontine glioma and their expression correlates with survival.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Brain Cancer ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Histone Genes ◽  
Histone H4 ◽  
Pontine Glioma ◽  
Histone H2b ◽  
Men And Women ◽  
Genes Encoding ◽  
Pediatric Brain ◽  
Median Survival Rate

Diffuse intrinsic pontine glioma is a pediatric brain cancer and has the lowest median survival rate of all cancers known to man (1). 99% of patients diagnosed with DIPG will expire within 5 years (1). Understanding the transcriptional behavior of tumors in DIPG is critical for the development of novel therapies. In this study, I compared the transcriptomes of tumors from men with DIPG versus that of tumors from women diagnosed with DIPG using a published dataset (2). I found that three histone genes, including HIST1H4C, HIST1H2BD, and HIST1H3D, which encode Histone H4, Histone H2B Type 1D, and Histone H3.1 were among the genes whose expression was most different between the DIPG tumors of men and women. Importantly, the expression level of two of these genes significantly correlated in a linear fashion with the amount of time the patient survived. It has previously been reported that 78% of DIPG tumors contain a mutation in Histone H3.1 (HIST1H3B) (3). This is the first report of differential expression of histone genes in tumors of patients with DIPG.

scholarly journals Iroquois transcription factors are perturbed in diffuse intrinsic pontine glioma.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Brain Cancer ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Differentially Expressed ◽  
Normal Brain ◽  
Pontine Glioma ◽  
Control Brain ◽  
Cancer Transcriptome ◽  
Tissue Of Origin ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
The Brain

The brain cancer diffuse intrinsic pontine glioma (DIPG) is the most fatal of all cancers with a 5-year survival rate of less than 1%, meaning greater than 99% of patients diagnosed with DIPG will expire within 5 years (1). Systems-level analyses of the cancer transcriptome compared to the tissue from which it arises presents a unique opportunity to gain insights into the transcriptional behavior of each cancer and how it differs from its tissue of origin (2). In this study I used published microarray data to compare the DIPG tumor transcirptomes to that of the normal brain (3). In both datasets, I found differential expression of an Iroquois transcription factor in DIPG tumors: in one dataset, IRX2, IRX5 and IRX3 were among the most differentially expressed genes in the tumors of patients with DIPG, and in a separate dataset, IRX4 was significantly differentially expressed when compared to control brain tissues. IRX proteins may be important molecules in the biology of diffuse intrinsic pontine gliomas.

scholarly journals Recurrent structural variations of lncRNA gene CCDC26 in diffuse intrinsic pontine glioma

2021 ◽  
Author(s):  
Lihua Zou
Keyword(s):  
Brain Cancer ◽  
Noncoding Rna ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Pontine Glioma ◽  
Structural Variations ◽  
Lncrna Gene ◽  
Elevated Expression ◽  
Pediatric Brain

AbstractWe report recurrent somatic structural variations (SVs) involving long noncoding RNA (lncRNA) CCDC26 in 13% of Diffuse Intrinsic Pontine Glioma (DIPG) patients. We validate our findings using whole genome sequencing data from two independent patient cohorts. CCDC26 SVs cause increased expression of CCDC26 gene in patients. In addition, CCDC26 expression is associated with elevated expression of MYC and proliferation signature. Our findings identify CCDC26 as a novel significantly mutated gene in DIPG and highlight the importance of structural variations in pediatric brain cancer.

scholarly journals The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation

2021 ◽  
Vol 22 (17) ◽  
pp. 9165
Author(s):  
David Roig-Carles ◽  
Holly Jackson ◽  
Katie F. Loveson ◽  
Alan Mackay ◽  
Rebecca L. Mather ◽  
...  
Keyword(s):  
Large Family ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Locked Nucleic Acid ◽  
Normal Brain ◽  
Pontine Glioma ◽  
Incurable Cancer ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of H19 lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs. normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in the up-regulation of oncogenic let-7 target (e.g., SULF2 and OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.

scholarly journals MR imaging features of diffuse intrinsic pontine glioma and relationship to overall survival: report from the International DIPG Registry

2020 ◽  
Vol 22 (11) ◽  
pp. 1647-1657 ◽  
Author(s):  
James L Leach ◽  
James Roebker ◽  
Austin Schafer ◽  
Joshua Baugh ◽  
Brooklyn Chaney ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariable Analysis ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Imaging Features ◽  
Pontine Glioma ◽  
Distant Disease ◽  
Mutation Status ◽  
Mri Features ◽  
Multivariable Analyses ◽  
Prospective Trials

Abtract Background This study describes imaging features of diffuse intrinsic pontine glioma (DIPG) and correlates with overall survival (OS) and histone mutation status in the International DIPG Registry (IDIPGR). Methods Four hundred cases submitted to the IDIPGR with a local diagnosis of DIPG and baseline MRI were evaluated by consensus review of 2 neuroradiologists; 43 cases were excluded (inadequate imaging or alternative diagnoses). Agreement between reviewers, association with histone status, and univariable and multivariable analyses relative to OS were assessed. Results On univariable analysis imaging features significantly associated with worse OS included: extrapontine extension, larger size, enhancement, necrosis, diffusion restriction, and distant disease. On central review, 9.5% of patients were considered not to have DIPG. There was moderate mean agreement of MRI features between reviewers. On multivariable analysis, chemotherapy, age, and distant disease were predictors of OS. There was no difference in OS between wild-type and H3 mutated cases. The only imaging feature associated with histone status was the presence of ill-defined signal infiltrating pontine fibers. Conclusions Baseline imaging features are assessed in the IDIPGR. There was a 9.5% discordance in DIPG diagnosis between local and central review, demonstrating need for central imaging confirmation for prospective trials. Although several imaging features were significantly associated with OS (univariable), only age and distant disease were significant on multivariable analyses. There was limited association of imaging features with histone mutation status, although numbers are small and evaluation exploratory.

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