Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.
Recommended Citation
Bredel M, Espinosa L, Kim H, Scholtens DM, McElroy JP, Rajbhandari R, Meng W, Kollmeyer TM, Malta TM, Quezada MA, Harsh GR, Lobo-Jarne T, Solé L, Merati A, Nagaraja S, Nair S, White JJ, Thudi NK, Fleming JL, Webb A, Natsume A, Ogawa S, Weber RG, Bertran J, Haque SJ, Hentschel B, Miller CR, Furnari FB, Chan TA, Grosu AL, Weller M, Barnholtz-Sloan JS, Monje M, Noushmehr H, Jenkins RB, Rogers CL, MacDonald DR, Pugh SL, and Chakravarti A. Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas. Cell Rep Med 2023; 4(6):101082.
Document Type
Article
Publication Date
6-20-2023
Publication Title
Cell Rep Med
Abstract
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.
Medical Subject Headings
Child; Humans; Brain Neoplasms; Epigenome; Glioma; Haploinsufficiency; Mutation; NF-KappaB Inhibitor alpha; Isocitrate Dehydrogenase
PubMed ID
37343523
Volume
4
Issue
6
First Page
101082
Last Page
101082
