دورية أكاديمية
Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.
| العنوان: | Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas. |
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| المؤلفون: | Bredel, Markus, Espinosa, Lluís, Kim, Hyunsoo, Scholtens, Denise M, McElroy, Joseph P, Rajbhandari, Rajani, Meng, Wei, Kollmeyer, Thomas M, Malta, Tathiane M, Quezada, Michael A, Harsh, Griffith R, Lobo-Jarne, Teresa, Solé, Laura, Merati, Aran, Nagaraja, Surya, Nair, Sindhu, White, Jaclyn J, Thudi, Nanda K, Fleming, Jessica L, Webb, Amy, Natsume, Atsushi, Ogawa, Seishi, Weber, Ruthild G, Bertran, Joan, Haque, S Jaharul, Hentschel, Bettina, Miller, C Ryan, Furnari, Frank B, Chan, Timothy A, Grosu, Anca-Ligia, Weller, Michael, Barnholtz-Sloan, Jill S, Monje, Michelle, Noushmehr, Houtan, Jenkins, Robert B, Rogers, C Leland, MacDonald, David R, Pugh, Stephanie L, Chakravarti, Arnab |
| المصدر: | Cell Rep Med ; ISSN:2666-3791 ; Volume:4 ; Issue:6 |
| بيانات النشر: | Elsevier Science |
| سنة النشر: | 2023 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | H3K27M mutation, IDH mutation, NFKBIA deletion, glioma, haploinsufficiency, methylome, nomogram, tumor suppressor |
| الوصف: | Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1016/j.xcrm.2023.101082Test; https://pubmed.ncbi.nlm.nih.gov/37343523Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314122Test/ |
| DOI: | 10.1016/j.xcrm.2023.101082 |
| الإتاحة: | https://doi.org/10.1016/j.xcrm.2023.101082Test https://pubmed.ncbi.nlm.nih.gov/37343523Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314122Test/ |
| حقوق: | Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. |
| رقم الانضمام: | edsbas.C66CDE3A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.xcrm.2023.101082 |
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