DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis

Sahm, Felix; Schrimpf, Daniel; Stichel, Damian; Jones, David; Hielscher, Thomas; Schefzyk, Sebastian; Okonechnikov, Konstantin; Koelsche, Christian; Reuß, David; Capper, David; Sturm, Dominik; Wirsching, Hans Georg; Berghoff, Anna Sophie; Baumgarten, Peter; Kratz, Annekathrin; Huang, Kristin; Wefers, Annika K.; Hovestadt, Volker; Sill, Martin; Ellis, Hayley Patricia; Kurian, Kathreena M.; Okuducu, Ali Fuat; Jungk, Christine; Drueschler, Katharina; Schick, Matthias; Bewerunge-Hudler, Melanie; Mawrin, Christian; Seiz-Rosenhagen, Marcel; Ketter, Ralf; Simon, Matthias; Westphal, Manfred; Lamszus, Katrin; Becker, Albert; Koch, Arend; Schittenhelm, Jens; Rushing, Elisabeth J.; Collins, V. Peter; Brehmer, Stefanie; Chávez, Lukas; Platten, Michael; Hänggi, Daniel; Unterberg, Andreas; Paulus, Werner; Wick, Wolfgang; Pfister, Stefan M.; Mittelbronn, Michel; Herold‐Mende, Christel; Weller, Michael; Deimling, Andreas von

doi:10.1016/s1470-2045(17)30155-9

Cited by 628 publications

(716 citation statements)

References 48 publications

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“…A number of mutations as well as DNA methylation profiles have all been shown to be linked with the risk of recurrence in meningioma. [58, 59] Addition of molecular markers has the potential to significantly improve not only understanding of the biology of meningioma, but refine prognostic and treatment stratification as well as development of more targeted treatment modalities. Importantly, this study has demonstrated that early recurrence/progression of atypical meningioma was significantly related to neurological outcomes.…”

Section: Discussionmentioning

confidence: 99%

Predictors of early progression of surgically treated atypical meningiomas

et al. 2018

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BackgroundClinical behaviour of atypical meningiomas is not uniform. While, as a group, they exhibit a high recurrence rate, some pursue a more benign course, whereas others progress early. We aim to investigate the imaging and pathological factors that predict risk of early tumour progression and to determine whether early progression is related to outcome.MethodsAdult patients with WHO grade II meningioma treated in three regional referral centres between 2007 and 2014 were included. MRI and pathology characteristics were assessed. Gross total resection (GTR) was defined as Simpson 1–3. Recurrence was classified into early and late (≤ 24 vs. > 24 months).ResultsAmong the 220 cases, 37 (16.8%) patients progressed within 24 months of operation. Independent predictors of early progression were subtotal resection (STR) (p = 0.005), parafalcine/parasagittal location (p = 0.015), peritumoural oedema (p = 0.027) and mitotic index (MI) > 7 (p = 0.007). Adjuvant radiotherapy was negatively associated with early recurrence (p = 0.046). Thirty-two per cent of patients with residual tumour and 26% after GTR received adjuvant radiotherapy. There was a significantly lower proportion of favourable outcomes at last follow-up (mRS 0–1) in patients with early recurrence (p = 0.001).ConclusionsAtypical meningiomas are a heterogeneous group of tumours with 16.8% patients having recurrence within 24 months of surgery. Residual tumour, parafalcine/parasagittal location, peritumoural oedema and a MI > 7 were all independently associated with early recurrence. As administration of adjuvant radiotherapy was not protocolised in this cohort, any conclusions about benefits of irradiation of WHO grade II meningiomas should be viewed with caution. Patients with early recurrence had worse neurological outcome. While histological and imaging characteristics provide some prognostic value, further molecular characterisation of atypical meningiomas is warranted to aid clinical decision making.

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Section: Discussionmentioning

confidence: 99%

Predictors of early progression of surgically treated atypical meningiomas

et al. 2018

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“…This hypomethylation, frequently seen early in cancer development, is commonly followed by locus-specific hypermethylation. Large-scale analyses have shown that DNA methylation aberrations are frequently present in cancers [9] and that DNA methylation profiling enables distinguishing cancer subtypes [10] and classifying cancers of unknown primary origin [11].A variety of DNA methylation aberrations have been suggested as biomarkers for early detection, prognostication and monitoring of cancer, including in noninvasive clinical material such as blood, stool, urine and bile. Great hopes are also tied to DNA methylation as a direct target for epigenetic therapy.…”

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confidence: 99%

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Details matter: the role of genomic location and assay standardization in DNA methylation analyses

Lind

Engeland

2017

Epigenomics

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Close to 60,000 papers mentioning DNA methylation have been published by April 2017, and more than 5000 of them were published last year alone [1]. This amounts to about 14 papers per day demonstrating an exploding interest for performing DNA methylation analyses. This is not surprising, considering the essential role DNA methylation plays in regulating gene expression [2], impacting essential processes such as cell differentiation. Inactivation of the DNA methyltransferases causes embryonic lethality in mice [3,4], underscoring the importance of correct DNA methylation patterns during normal development, with implications not only in health, but also disease.Aberrant DNA methylation has been reported in, for example, cardiovascular [5], neurodegenerative [6] and metabolic [7] disease. A link between DNA methylation and cancer was demonstrated as early as 1983, when a substantial proportion of CpG sites that were methylated in normal tissues were found to be unmethylated in cancer cells [8]. This hypomethylation, frequently seen early in cancer development, is commonly followed by locus-specific hypermethylation. Large-scale analyses have shown that DNA methylation aberrations are frequently present in cancers [9] and that DNA methylation profiling enables distinguishing cancer subtypes [10] and classifying cancers of unknown primary origin [11].A variety of DNA methylation aberrations have been suggested as biomarkers for early detection, prognostication and monitoring of cancer, including in noninvasive clinical material such as blood, stool, urine and bile. Great hopes are also tied to DNA methylation as a direct target for epigenetic therapy. Technological advancements, including genome-wide profiling of DNA methylation aberrations in groups of diseased individuals and healthy controls, are supporting a steady increase in the number of DNA methylation based biomarkers, especially for cancer.However, despite the enormous amount of papers that are being published on DNA methylation, hardly any of these findings enter routine clinical practice. This low success rate can be explained by the observation that the DNA methylation marker field suffers from general methodological issues that affect biomedical and biomarker research, such as insufficiently stringent methodology, low-quality reporting (including lack of adherence to reporting guidelines such as CONSORT, STARD, "Only when including quality and standardization at every level of DNA methylation analyses, will we be able to achieve the robustness to independently validate DNA methylation analyses and to compare multiple methylation studies in systematic reviews. This is the only way to more efficiently develop future DNA methylation based biomarkers."Manon van Engeland

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“…Following surgical resection, the designation of a WHO histological grade provides prognostic information and determines a potential indication for adjuvant therapy. Reassuringly, 80% of meningiomas show benign clinical behaviour and can be cured with resection alone, particularly those in favourable accessible locations 7. Benign WHO Grade I meningiomas have a five year overall survival of over 80%, and after a complete resection, the 10 year recurrence for grade I meningiomas varies from 20% to 39% 9…”

Section: Discussionmentioning

confidence: 99%