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

2020 ◽  
Author(s):  
Shahan Mamoor

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.

2021 ◽  
Author(s):  
Rucha ◽  
Vijay S

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.


2021 ◽  
Author(s):  
Henley Castillo ◽  
Kenzie Mellor ◽  
Amelia-Mae Marks ◽  
Willard L

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.


2020 ◽  
Author(s):  
Shahan Mamoor

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.


2020 ◽  
Author(s):  
Shahan Mamoor

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.


2021 ◽  
Author(s):  
Lihua Zou

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.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii294-iii295
Author(s):  
Jovana Pavisic ◽  
Chankrit Sethi ◽  
Chris Jones ◽  
Stergios Zacharoulis ◽  
Andrea Califano

Abstract Diffuse intrinsic pontine glioma (DIPG) remains a fatal disease with no effective drugs to date. Mutation-based precision oncology approaches are limited by lack of targetable mutations and genetic heterogeneity. We leveraged systems biology methodologies to discover common targetable disease drivers—master regulator proteins (MRs)—in DIPG to expand treatment options. Using the metaVIPER algorithm, we interrogated an integrated low grade glioma and GBM gene regulatory network with 31 DIPG-gene expression signatures to identify tumor-specific MRs by differential expression of their transcriptional targets. Unsupervised clustering identified MR signatures of upregulated activity in RRM2/TOP2A in 13 patients, CD3D in 5 patients, and MMP7, TACSTD2, RAC2 and SLC15A1/SLC34A2 in individual patients, all of which can be targeted. Notably, intratumoral administration of etoposide by convection enhanced delivery was effective in murine proneural gliomas in which TOP2 was identified as a MR while RRM2—targetable by drugs such as cladribine—has been shown to be a positive regulator of glioma progression whose knock-down inhibits tumor growth. We also prioritized drugs by their ability to reverse MR-activity signatures using a large drug-perturbation database. Patients clustered by predicted drug sensitivities with distinct groups of tumors predicted to respond to proteasome inhibitors, Thiotepa or Volasertib all of which have early evidence in treating gliomas. We will refine this analysis in a multi-institutional study of >100 patient gene expression profiles to define MR signatures driving known biological/molecular disease subtypes, use DIPG cell lines recapitulating common MR architectures to optimize therapy prioritization, and validate our findings in vivo.


Author(s):  
Anju Karki ◽  
Noah E Berlow ◽  
Jin-Ah Kim ◽  
Esther Hulleman ◽  
Qianqian Liu ◽  
...  

Abstract Background Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric cancer with unmet clinical need. DIPG is invasive in nature, where tumor cells interweave into the fiber nerve tracts of the pons making the tumor unresectable. Accordingly, novel approaches in combating the disease is of utmost importance and receptor-driven cell invasion in the context of DIPG is under-researched area. Here we investigated the impact on cell invasion mediated by PLEXINB1, PLEXINB2, platelet growth factor receptor (PDGFR)α, PDGFRβ, epithelial growth factor receptor (EGFR), activin receptor 1 (ACVR1), chemokine receptor 4 (CXCR4) and NOTCH1. Methods We used previously published RNA-sequencing data to measure gene expression of selected receptors in DIPG tumor tissue versus matched normal tissue controls (n=18). We assessed protein expression of the corresponding genes using DIPG cell culture models. Then, we performed cell viability and cell invasion assays of DIPG cells stimulated with chemoattractants/ligands. Results RNA-sequencing data showed increased gene expression of receptor genes such as PLEXINB2, PDGFRα, EGFR, ACVR1, CXCR4 and NOTCH1 in DIPG tumors compared to the control tissues. Representative DIPG cell lines demonstrated correspondingly increased protein expression levels of these genes. Cell viability assays showed minimal effects of growth factors/chemokines on tumor cell growth in most instances. Recombinant SEMA4C, SEM4D, PDGF-AA, PDGF-BB, ACVA, CXCL12 and DLL4 ligand stimulation altered invasion in DIPG cells. Conclusions We show that no single growth factor-ligand pair universally induces DIPG cell invasion. However, our results reveal a potential to create a composite of cytokines or anti-cytokines to modulate DIPG cell invasion.


2010 ◽  
Vol 187 (1-3) ◽  
pp. 120-123 ◽  
Author(s):  
Huang-Quan Lin ◽  
Roy Choi ◽  
Kam-Leung Chan ◽  
Denis Ip ◽  
Karl Wah-keung Tsim ◽  
...  

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