Next generation sequencing impacts the classification and management of primary brain tumours

Cheung, Veronica; Buckland, Michael E.; Wei, Grace; Lee, Maggie; Sy, Joanne

doi:10.1016/j.pathol.2020.12.008

Cited by 2 publications

(2 citation statements)

References 7 publications

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“…Complete molecular characterization required IDH1 codon 132 and IDH2 codon 172 sequencing if IDH1-R132H immunohistochemistry was negative, and determination of 1p/19q-codeletion status for patients with IDH mutation detected by any method. For patients without complete molecular characterization based on existing data, next-generation sequencing (NGS) was performed to determine IDH and 1p/19q-codeletion status, utilizing previously reported methodology [ 19 ]. For patients undergoing NGS, the output also included TERT promoter variant status, + 7/ − 10 and EGFR copy number status according to the updated criteria for glioblastoma in WHO 2021 [ 4 ].…”

Section: Methodsmentioning

confidence: 99%

Conventional MRI features can predict the molecular subtype of adult grade 2–3 intracranial diffuse gliomas

et al. 2022

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Purpose Molecular biomarkers are important for classifying intracranial gliomas, prompting research into correlating imaging with genotype (“radiogenomics”). A limitation of the existing radiogenomics literature is the paucity of studies specifically characterizing grade 2–3 gliomas into the three key molecular subtypes. Our study investigated the accuracy of multiple different conventional MRI features for genotype prediction. Methods Grade 2–3 gliomas diagnosed between 2007 and 2013 were identified. Two neuroradiologists independently assessed nine conventional MRI features. Features with better inter-observer agreement (κ ≥ 0.6) proceeded to consensus assessment. MRI features were correlated with genotype, classified as IDH-mutant and 1p/19q-codeleted (IDHmut/1p19qcodel), IDH-mutant and 1p/19q-intact (IDHmut/1p19qint), or IDH-wildtype (IDHwt). For IDHwt tumors, additional molecular markers of glioblastoma were noted. Results One hundred nineteen patients were included. T2-FLAIR mismatch (stratified as > 50%, 25–50%, or < 25%) was the most predictive feature across genotypes (p < 0.001). All 30 tumors with > 50% mismatch were IDHmut/1p19qint, and all seven with 25–50% mismatch. Well-defined margins correlated with IDHmut/1p19qint status on univariate analysis (p < 0.001), but this related to correlation with T2-FLAIR mismatch; there was no longer an association when considering only tumors with < 25% mismatch (p = 0.386). Enhancement (p = 0.001), necrosis (p = 0.002), and hemorrhage (p = 0.027) correlated with IDHwt status (especially “molecular glioblastoma”). Calcification correlated with IDHmut/1p19qcodel status (p = 0.003). A simple, step-wise algorithm incorporating these features, when present, correctly predicted genotype with a positive predictive value 91.8%. Conclusion T2-FLAIR mismatch strongly predicts IDHmut/1p19qint even with a lower threshold of ≥ 25% mismatch and outweighs other features. Secondary features include enhancement, necrosis and hemorrhage (predicting IDHwt, especially “molecular glioblastoma”), and calcification (predicting IDHmut/1p19qcodel).

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Section: Methodsmentioning

confidence: 99%

Conventional MRI features can predict the molecular subtype of adult grade 2–3 intracranial diffuse gliomas

et al. 2022

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“…All patients had next generation sequencing (NGS) [ 26 ] or IDH pyrosequencing to determine IDH status, unless an IDH1-R132H mutation had already been demonstrated by immunohistochemistry as part of routine clinical practice or previous research. IDH mutations were thus divided into IDH1-R132H (based on sequencing or positive immunohistochemistry) or non-canonical (all IDH1 and IDH2 mutations other than IDH1-R132H).…”

Section: Methodsmentioning

confidence: 99%

Correlating MRI features with additional genetic markers and patient survival in histological grade 2-3 IDH-mutant astrocytomas

Lasocki,

Buckland,

Molinaro

et al. 2023

Neuroradiology

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Purpose The increasing importance of molecular markers for classification and prognostication of diffuse gliomas has prompted the use of imaging features to predict genotype (“radiogenomics”). CDKN2A/B homozygous deletion has only recently been added to the diagnostic paradigm for IDH[isocitrate dehydrogenase]-mutant astrocytomas; thus, associated radiogenomic literature is sparse. There is also little data on whether different IDH mutations are associated with different imaging appearances. Furthermore, given that molecular status is now generally obtained routinely, the additional prognostic value of radiogenomic features is less clear. This study correlated MRI features with CDKN2A/B status, IDH mutation type and survival in histological grade 2-3 IDH-mutant brain astrocytomas. Methods Fifty-eight grade 2–3 IDH-mutant astrocytomas were identified, 50 with CDKN2A/B results. IDH mutations were stratified into IDH1-R132H and non-canonical mutations. Background and survival data were obtained. Two neuroradiologists independently assessed the following MRI features: T2-FLAIR mismatch (<25%, 25–50%, >50%), well-defined tumour margins, contrast-enhancement (absent, wispy, solid) and central necrosis. Results 8/50 tumours with CDKN2A/B results demonstrated homozygous deletion; slightly shorter survival was not significant (p=0.571). IDH1-R132H mutations were present in 50/58 (86%). No MRI features correlated with CDKN2A/B status or IDH mutation type. T2-FLAIR mismatch did not predict survival (p=0.977), but well-defined margins predicted longer survival (HR 0.36, p=0.008), while solid enhancement predicted shorter survival (HR 3.86, p=0.004). Both correlations remained significant on multivariate analysis. Conclusion MRI features did not predict CDKN2A/B homozygous deletion, but provided additional positive and negative prognostic information which correlated more strongly with prognosis than CDKN2A/B status in our cohort.

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Next generation sequencing impacts the classification and management of primary brain tumours

Cited by 2 publications

References 7 publications

Conventional MRI features can predict the molecular subtype of adult grade 2–3 intracranial diffuse gliomas

Conventional MRI features can predict the molecular subtype of adult grade 2–3 intracranial diffuse gliomas

Correlating MRI features with additional genetic markers and patient survival in histological grade 2-3 IDH-mutant astrocytomas

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