دورية أكاديمية
METABOLOGENOMIC CHARACTERIZATION UNCOVERS HETEROGENEITY AMONG IDH MUTANT GLIOMAS
| العنوان: | METABOLOGENOMIC CHARACTERIZATION UNCOVERS HETEROGENEITY AMONG IDH MUTANT GLIOMAS |
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| المؤلفون: | Ajisebutu, Andrew, Nassiri, Farshad, Wang, Justin Z, Mamatjan, Yasin, Nejad, Romina, Patil, Vikas, Liu, Jeff, Voisin, Mathew R, Mansouri, Sheila, Karimi, Shirin, Chakravarthy, Ankur, Chen, Eric, De Carvalho, Daniel D, Aldape, Kenneth, Zadeh, Gelareh |
| المصدر: | Neuro-Oncology Advances ; volume 5, issue Supplement_2, page i1-i1 ; ISSN 2632-2498 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Surgery, Oncology, Neurology (clinical) |
| الوصف: | Mutations in isocitrate dehydrogenase (IDH) enzymes are recognised to drive the molecular footprint of diffuse gliomas, and patients with IDH-mutant gliomas have overall favorable outcomes compared to patients with IDH wildtype tumors. Nonetheless, survival can vary widely even amongst patients with IDH-mutant tumors. A comprehensive metabologenomic characterization of IDH-mutant gliomas has not been performed to date. METHOD: Glioma samples from a cohort of 154 patients that underwent surgery at the UHN in Toronto, ON, underwent multiplatform molecular analysis, including metabolomic studies, genome- wide DNA methylation profiling and bulk RNA sequencing. A comprehensive, integrative analysis was performed, and validated through the use of an independent cohort derived from The Cancer Genome Atlas. RESULTS: We discovered a group of IDH-mutant gliomas with globally altered metabolism that highly resembled IDH wildtype tumors. Notably, these IDH-mutant gliomas with dysregulated metabolism were distinguished from their IDH-mutant counterparts by significantly shorter overall survival. The prognostic relevance of dysregulated metabolism complements, but was not wholly explained by canonically recognized prognostic classifications in IDH-mutant gliomas including 1p/19q codeletion, glioma CpG Island Hypermethylator (GCIMP) status and CDKN2A homozygous deletion. IDH-mutant tumors with dysregulated metabolism harbored distinct epigenetic alterations that converged to drive proliferative and stem-like transcriptional profiles. CONCLUSION: Utilizing a cross-platform analysis we have uncovered a novel subtyping of IDH-mutant gliomas with dysregulated cellular metabolism with similar survival to IDH-wildtype tumors. The metabolic profile provides unique information on glioma phenotypes, which may can facilitate a more comprehensive understanding of glioma biology, and provide a window to target novel dependencies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/noajnl/vdad071.001 |
| الإتاحة: | https://doi.org/10.1093/noajnl/vdad071.001Test https://academic.oup.com/noa/article-pdf/5/Supplement_2/i1/50860392/vdad071.001.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.B1F8BE72 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/noajnl/vdad071.001 |
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