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000136672 1001_ $$aCavalli, Florence M G$$b0
000136672 245__ $$aHeterogeneity within the PF-EPN-B ependymoma subgroup.
000136672 260__ $$aBerlin$$bSpringer$$c2018
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000136672 520__ $$aPosterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies.
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000136672 7001_ $$0P:(DE-He78)a8c698e0904394407c5261932915daa5$$aHübner, Jens-Martin$$b1$$eFirst author
000136672 7001_ $$0P:(DE-He78)36e1ec4777d5b7887344177dca41eae9$$aSharma, Tanvi$$b2$$eFirst author
000136672 7001_ $$aLuu, Betty$$b3
000136672 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b4
000136672 7001_ $$aZapotocky, Michal$$b5
000136672 7001_ $$aMack, Stephen C$$b6
000136672 7001_ $$0P:(DE-He78)046fd145f1008f83f6236580727bbc0f$$aWitt, Hendrik$$b7
000136672 7001_ $$aLin, Tong$$b8
000136672 7001_ $$aShih, David J H$$b9
000136672 7001_ $$aHo, Ben$$b10
000136672 7001_ $$aSanti, Mariarita$$b11
000136672 7001_ $$aEmery, Lyndsey$$b12
000136672 7001_ $$aHukin, Juliette$$b13
000136672 7001_ $$aDunham, Christopher$$b14
000136672 7001_ $$aMcLendon, Roger E$$b15
000136672 7001_ $$aLipp, Eric S$$b16
000136672 7001_ $$aGururangan, Sridharan$$b17
000136672 7001_ $$aGrossbach, Andrew$$b18
000136672 7001_ $$aFrench, Pim$$b19
000136672 7001_ $$aKros, Johan M$$b20
000136672 7001_ $$avan Veelen, Marie-Lise C$$b21
000136672 7001_ $$aRao, Amulya A Nageswara$$b22
000136672 7001_ $$aGiannini, Caterina$$b23
000136672 7001_ $$aLeary, Sarah$$b24
000136672 7001_ $$aJung, Shin$$b25
000136672 7001_ $$aFaria, Claudia C$$b26
000136672 7001_ $$aMora, Jaume$$b27
000136672 7001_ $$aSchüller, Ulrich$$b28
000136672 7001_ $$aAlonso, Marta M$$b29
000136672 7001_ $$aChan, Jennifer A$$b30
000136672 7001_ $$aKlekner, Almos$$b31
000136672 7001_ $$aChambless, Lola B$$b32
000136672 7001_ $$aHwang, Eugene I$$b33
000136672 7001_ $$aMassimino, Maura$$b34
000136672 7001_ $$aEberhart, Charles G$$b35
000136672 7001_ $$aKarajannis, Matthias A$$b36
000136672 7001_ $$aLu, Benjamin$$b37
000136672 7001_ $$aLiau, Linda M$$b38
000136672 7001_ $$aZollo, Massimo$$b39
000136672 7001_ $$aFerrucci, Veronica$$b40
000136672 7001_ $$aCarlotti, Carlos$$b41
000136672 7001_ $$aTirapelli, Daniela P C$$b42
000136672 7001_ $$aTabori, Uri$$b43
000136672 7001_ $$aBouffet, Eric$$b44
000136672 7001_ $$aRyzhova, Marina$$b45
000136672 7001_ $$aEllison, David W$$b46
000136672 7001_ $$aMerchant, Thomas E$$b47
000136672 7001_ $$aGilbert, Mark R$$b48
000136672 7001_ $$aArmstrong, Terri S$$b49
000136672 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b50
000136672 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b51
000136672 7001_ $$aTaylor, Michael D$$b52
000136672 7001_ $$aAldape, Kenneth$$b53
000136672 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b54
000136672 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b55$$eLast author
000136672 7001_ $$00000-0002-6557-895X$$aRamaswamy, Vijay$$b56
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