Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Profiling genome-wide DNA methylation patterns provides an alternative to the World Health Organization (WHO) classification for meningioma, offering a more accurate prediction of prognosis and recurrence, suggests research published in The Lancet Oncology.
“The approach presented here is potentially very useful for stratifying meningioma patients to observation-only or adjuvant treatment groups”, say Andreas von Deimling, from the University of Heidelberg in Germany, and co-authors.
“We consider methylation-based tumour classification highly relevant for the future diagnosis and treatment of meningioma”, they write.
Genome-wide DNA methylation profiling clearly segregated 497 meningioma samples collected at 10 European neuro-oncology centres from 309 samples of other extra-axial skull tumours that may mimic meningioma histologically, such as Schwannoma and chordoma.
Moreover, the unsupervised clustering of DNA methylation divided the meningioma samples into epigenetic groups, with four methylation classes in group A (three benign classes and one intermediate-A) and two in group B (intermediate-B and malignant).
“This strong separation suggests either the existence of distinct cells of origin or an underlying event with a major effect on genome-wide DNA methylation”, the researchers hypothesise.
They continue: “Moreover, the fact that patients with meningiomas clustered in group A share a mainly benign clinical course, with a small proportion showing an intermediate clinical course, and that patients with meningiomas of group B follow an intermediate to malignant clinical course, might further argue towards a distinct cell of origin with different intrinsic propensities for malignant transformation.”
The group A classes included WHO grade I tumours and group B was populated with WHO grade III tumours, while grade II tumours were found across all the methylation classes, the team explains.
And the group classification was consistent when assessed in 37 pairs of primary and recurrent tumour samples, “supporting further assessment of methylation profiling for diagnostic and prognostic implications”, the authors say.
Further analysis of 53 genes previously reported as mutated in meningioma in 303 of the samples revealed that recurrent mutations were each significantly enriched in some but not all of the methylation classes
Furthermore, when methylation was examined in combination with histology, the researchers identified two patterns – that a methylation class was “strongly” linked to a single histological subtype or small set of subtypes, or that a methylation class or subtype was “widely spread” across histology variants.
Progression-free survival (PFS) was assessed for 228 of the meningioma samples by methylation class and this revealed that both individual and grouped methylation classes gave “more precise” prediction of PFS at 10 years than the WHO grade.
Furthermore, the researchers found that stratifying by methylation class gave a more accurate prediction of patient outcome than WHO grade alone, “showing the benefit of methylation class-based grading for patients and the potential to greatly reduce undertreatment or overtreatment.”
The authors of an accompanying comment describe the study as a “milestone in the molecular landscape” of meningiomas, adding that the findings “reaffirm the importance of epigenetic changes in brain tumours (as has been previously shown for gliomas) and substantiate the results of previous mutational studies”.
However, Marc Sanson and Michel Kalamarides, from Sorbonne Universités in Paris, France, say that the “practical consequences” of the methylation classification used in the study “remain limited” because of the lack of randomised trials for postoperative therapy in atypical meningioma.
“In the same way as has been done for gliomas in the past decade, classification and management of meningiomas should be revisited in the near future and modulated by the integration of genomic, epigenetic, and expression data”, they advise.
Sahm F, Schrimpf D, Stichel D, et al. DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol; Advance online publication 14 March 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30155-9
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