Imaging Correlates of Adult Glioma Genotypes

Abstract

Primary brain tumors, most commonly gliomas, are histopathologically typed and graded as World Health Organization (WHO) grades I-IV according to increasing degrees of malignancy. These grades provide prognostic information and guidance on treatment such as radiation therapy and chemotherapy after surgery. Despite the confirmed value of the WHO grading system, results of a multitude of studies and prospective interventional trials now indicate that tumors with identical morphologic criteria can have highly different outcomes. Molecular markers can allow subtypes of tumors of the same morphologic type and WHO grade to be distinguished and are, therefore, of great interest in personalization of brain tumor treatment. Recent genomic-wide studies have resulted in a far more comprehensive understanding of the genomic alterations in gliomas and provide suggestions for a new molecularly based classification. Magnetic resonance (MR) imaging phenotypes can serve as noninvasive surrogates for tumor genotypes and can provide important information for diagnosis, prognosis, and, eventually, personalized treatment. The newly emerged field of radiogenomics allows specific MR imaging phenotypes to be linked with gene expression profiles. In this article, the authors review the conventional and advanced imaging features of three tumoral genotypes with prognostic and therapeutic consequences: (a) isocitrate dehydrogenase mutation; (b) the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19, or 1p19q codeletion; and (c) methylguanine methyltransferase promoter methylation. RSNA, 2017.

Conventional and advanced magnetic resonance imaging in patients with high-grade glioma

“…There are three isoforms of the IDH gene, the most important mutations of which involve cytosolic IDH1 and the mitochondrial IDH2 forms; the majority of IDH mutants in glioma are IDH1 mutations. 72 …”

Molecular classification of patients with grade II/III glioma using quantitative MRI characteristics

“…Finally, in an exploratory analysis, we examine our quantitative imaging features in patients who are MGMT methylated versus unmethylated. Based on our previous work [35] and other published studies [36], we hypothesize that: (1) measures of FLAIR heterogeneity will be greater in patients with IDH-wt compared to IDH-mt tumors. In those with IDH-mt tumor, we hypothesize that heterogeneity will be greater in 1p/19q-codeleted tumors compared to those with 1p/19q-intact tumors; (2) FLAIR borders will be less distinct in patients with IDH-wt compared to IDH-mt tumors.…”

MR Elastography Analysis of Glioma Stiffness andIDH1-Mutation Status

“…The WHO classification was updated in 2016 to include molecular markers, which have significant implications for patient outcome and may be critical information in the selection of a treatment strategy. Recent efforts in the area of radiogenomics have explored the potential of utilizing MR imaging phenotypes to noninvasively determine tumor genotypes, including the detection of three common genomic alterations in glioma 4 . Mutations in the gene responsible for encoding a metabolic enzyme called isocitrate dehydrogenase 1 ( IDH1 ) frequently occur in low grade gliomas, exhibiting different genetic and epigenetic etiology when compared to IDH1 wild-type gliomas and are considered a distinct disease entity with a poorer prognosis, independent of tumor grade 5, 6 .…”