Identification of novel therapeutic targets for histone 3 mutated children’s brain tumour, using unique tumour cell surface proteomic signatures
| العنوان: | Identification of novel therapeutic targets for histone 3 mutated children’s brain tumour, using unique tumour cell surface proteomic signatures |
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| المؤلفون: | Ruman Rahman, Farhana Haque, Richard Grundy, Anya Snary, Robert Layfield |
| المصدر: | Neuro-Oncology. 23:iv9-iv9 |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Mutation, Cell, Biology, medicine.disease_cause, Proteomics, medicine.disease, Cell membrane, Histone H3, medicine.anatomical_structure, Histone, Oncology, Cell culture, Glioma, medicine, biology.protein, Cancer research, Neurology (clinical) |
| الوصف: | Aims Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. We hypothesized that the histone 3 mutant tumours will have distinct mutation specific surfactome (cell membrane proteins) signature. Method We therefore analysed the cell surface proteomics of pHGG and DIPG, in order to identify novel targets for therapy. We have at first isolated the cell membrane fractions from a range of patient cells carrying different histone 3 mutations (G34R, G34V), relative to wild type histone 3. A comparative quantitative mass-spectrometry analyses of these cell surface membrane fractions is then performed. Results The results obtained to date demonstrated unique differential cell membrane expression patterns which correlated to specific mutation type. For example, increased expression of Ras-related proteins Rab-3, Rab-3D is detected only in histone H3.3-G34R mutated cell line in comparison. Conclusion Identification and analyses of these unique cell membrane proteins’ association with specific in H3.3 mutation in pHGG, will help to identify precise mutation specific therapeutic targets, benefiting the patients to receive therapy based on tumour’s molecular signature. |
| تدمد: | 1523-5866 1522-8517 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::d58f1ec243ca7f196a3eabd13ad08f16Test https://doi.org/10.1093/neuonc/noab195.019Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........d58f1ec243ca7f196a3eabd13ad08f16 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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