A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

Pappula, Amrit L; Rasheed, Shayaan; Mirzaei, Golrokh; Petreaca, Ruben C.; Bouley, Renee

doi:10.3390/cancers13174299

Cited by 22 publications

(24 citation statements)

References 128 publications

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“…Similar to our findings, Pappula et al . identified the 4637 differentially expressed genes (DEGs) between IDH1-mutant and IDH1-wild-type astrocytoma patients, and 18 OR genes including OR4N2 (mouse Olfr733) belonged to the DEGs ( 58 ). The distinct expression of ORs in the three glioma subtypes implies that ORs might participate in tumor formation and in the construction of the tumor microenvironment during gliomagenesis.…”

Section: Main Textmentioning

confidence: 99%

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review

Cho

Koo

2021

BMB Rep

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Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in ＞ 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma. [

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Section: Main Textmentioning

confidence: 99%

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review

Cho

Koo

2021

BMB Rep

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“…This particular substitution produces a metabolic byproduct that appears to increase the oncogenic potential of gliomas by interfering with histone demethylases and increasing oxidative species-related DNA damage [ 59 ]. Perhaps counterintuitively, the presence of this mutation is associated with better prognoses compared with glioma patients with a wildtype IDH1 [ 60 , 61 , 62 , 63 ]. This appears to be related to the low NADPH production levels in IDH1 mutant cells which renders patients sensitive to therapy [ 64 ].…”

Section: Resultsmentioning

confidence: 99%

Arginine Depletion in Human Cancers

Nelakurti

Rossetti

Husbands

et al. 2021

Cancers

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Arginine is encoded by six different codons. Base pair changes in any of these codons can have a broad spectrum of effects including substitutions to twelve different amino acids, eighteen synonymous changes, and two stop codons. Four amino acids (histidine, cysteine, glutamine, and tryptophan) account for over 75% of amino acid substitutions of arginine. This suggests that a mutational bias, or “purifying selection”, mechanism is at work. This bias appears to be driven by C > T and G > A transitions in four of the six arginine codons, a signature that is universal and independent of cancer tissue of origin or histology. Here, we provide a review of the available literature and reanalyze publicly available data from the Catalogue of Somatic Mutations in Cancer (COSMIC). Our analysis identifies several genes with an arginine substitution bias. These include known factors such as IDH1, as well as previously unreported genes, including four cancer driver genes (FGFR3, PPP6C, MAX, GNAQ). We propose that base pair substitution bias and amino acid physiology both play a role in purifying selection. This model may explain the documented arginine substitution bias in cancers.

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“…An association between IDH1 mutations and reduced ATRX expression has also been shown. Mutations in CHK2 are instead associated with an IDH1-wildtype astrocytoma [ 25 ]. Núñez et al discovered that mutant IDH1 helps maintain genomic stability in tumors by enhancing the DDR [ 26 ].…”

Section: Targeting Ddr Pathways In Gbmentioning

confidence: 99%

Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma

Everix

Nair

Driver

et al. 2022

Cancers

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Despite numerous innovative treatment strategies, the treatment of glioblastoma (GB) remains challenging. With the current state-of-the-art therapy, most GB patients succumb after about a year. In the evolution of personalized medicine, targeted radionuclide therapy (TRT) is gaining momentum, for example, to stratify patients based on specific biomarkers. One of these biomarkers is deficiencies in DNA damage repair (DDR), which give rise to genomic instability and cancer initiation. However, these deficiencies also provide targets to specifically kill cancer cells following the synthetic lethality principle. This led to the increased interest in targeted drugs that inhibit essential DDR kinases (DDRi), of which multiple are undergoing clinical validation. In this review, the current status of DDRi for the treatment of GB is given for selected targets: ATM/ATR, CHK1/2, DNA-PK, and PARP. Furthermore, this review provides a perspective on the use of radiopharmaceuticals targeting these DDR kinases to (1) evaluate the DNA repair phenotype of GB before treatment decisions are made and (2) induce DNA damage via TRT. Finally, by applying in-house selection criteria and analyzing the structural characteristics of the DDRi, four drugs with the potential to become new therapeutic GB radiopharmaceuticals are suggested.

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A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

Cited by 22 publications

References 128 publications

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review

Arginine Depletion in Human Cancers

Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma

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