Acquired somatic mutations of IDH1 and IDH2 have recently been reported in some types of brain tumors and a small proportion of acute myeloid leukemia (AML) cases.
Our findings indicate that CDKN2A/B risk genotypes are associated with primary glioblastoma without IDH mutation, and that there is an inverse association between RTEL1 risk genotypes and 1p/19q codeletion, suggesting that these genetic variants have a molecular impact on the genesis of high graded brain tumors.
There is growing interest in identification of diagnostic, prognostic or predictive blood biomarkers in CNS tumor patients, and emerging studies indicate that certain brain tumors are indeed associated with distinct profiles of circulating factors such as proteins (e.g., glial fibrillary acidic protein), DNA fragments (e.g., containing mutated IDH) or miRNAs (e.g., miRNA-21).
IDH mutation screening is rapidly becoming part of the routine pathological work up of human brain tumors, providing both diagnostic and prognostic information.
In this study, we address this need by presenting a proton magnetic resonance spectroscopy ((1)H-MRS) acquisition scheme that uses an ultrahigh magnetic field (≥ 7T) capable of noninvasively detecting 2-HG with quantitative measurements sufficient to differentiate mutant cytosolic IDH1 and mitochondrial IDH2 in human brain tumors.
We first demonstrated identical IDH mutations in the brain tumor samples from various locations in this patient, but different 1p,19q results by fluorescent in-situ hybridization, different whole genome copy number profiles by OncoScan analysis, and a discrepant IDH2M131I mutation unique to one tumor, supporting a multifocal disease process in the setting of somatic IDH mosaicism.
Together, these findings (1) show that IDH mutation status is associated with a distinct angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging and (2) highlight the potential future of radiogenomics (i.e. the correlation between cancer imaging and genomic features) towards a more accurate diagnostic workup of brain tumors.
The aim of this study is to investigate in depth the prevalence of non-R132HIDH ("non-canonical") mutations in brain tumors classified according to the 2016 WHO scheme and their clonal distribution in neoplastic cells.
The new 2016 WHO brain tumor classification defines different diffuse gliomas primarily according to the presence or absence of IDH mutations ( IDH-mt) and combined 1p/19q loss.
We used human glioma tissues and derived brain tumor stem cells (BTSCs) to study the expression of HIF1α target genes in IDH mutant ((mt)) and IDH wild-type ((wt)) tumors.
IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group.