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000186390 041__ $$aEnglish
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000186390 1001_ $$0P:(DE-He78)3de637452ba900e2bdd359b8f41953bf$$aEcker, Jonas$$b0$$eFirst author$$udkfz
000186390 245__ $$aMolecular diagnostics enables detection of actionable targets: the Pediatric Targeted Therapy 2.0 registry.
000186390 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2023
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000186390 520__ $$aPrecision oncology requires diagnostic accuracy and robust detection of actionable alterations. The Pediatric Targeted Therapy (PTT) 2.0 program aims at improving diagnostic accuracy by addition of molecular analyses to the existing histological diagnosis and detection of actionable alterations for relapsed paediatric oncology patients, in cases with limited availability of tumour material.Paediatric patients diagnosed with relapse or progression of a central nervous system tumour (n = 178), a sarcoma (n = 41) or another solid tumour (n = 44) were included. DNA methylation array, targeted gene panel sequencing on tumour and blood (130 genes), RNA sequencing in selected cases and a pathway-specific immunohistochemistry (IHC) panel were performed using limited formalin-fixed paraffin embedded tissue from any disease episode available. The clinical impact of reported findings was assessed by a serial questionnaire-based follow-up.Integrated molecular diagnostics resulted in refined or changed diagnosis in 117/263 (44%) tumours. Actionable targets were detected in 155/263 (59%) cases. Constitutional DNA variants with clinical relevance were identified in 16/240 (7%) of patients, half of which were previously unknown. Clinical follow-up showed that 26/263 (10%) of patients received mechanism-of-action based treatment matched to the molecular findings.Next-generation diagnostics adds robust and relevant information on diagnosis, actionable alterations and cancer predisposition syndromes even when tissue from the current disease episode is limited.
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000186390 650_7 $$2Other$$aBrain tumour
000186390 650_7 $$2Other$$aCancer predisposition
000186390 650_7 $$2Other$$aConstitutional DNA variant
000186390 650_7 $$2Other$$aMolecular diagnostics
000186390 650_7 $$2Other$$aMolecular targeted therapy
000186390 650_7 $$2Other$$aPaediatric oncology
000186390 650_7 $$2Other$$aPrecision oncology
000186390 650_7 $$2Other$$aSarcoma
000186390 7001_ $$0P:(DE-He78)a23e88cc676489fe05be8c178ceaf58e$$aSelt, Florian$$b1$$udkfz
000186390 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b2$$udkfz
000186390 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b3$$udkfz
000186390 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b4$$udkfz
000186390 7001_ $$0P:(DE-He78)5e3d4de4b59cd068969e101847794267$$aHirsch, Steffen$$b5$$udkfz
000186390 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b6$$udkfz
000186390 7001_ $$aDikow, Nicola$$b7
000186390 7001_ $$aSutter, Christian$$b8
000186390 7001_ $$0P:(DE-He78)7b8ffa9edd8dab810fd31583df374ec3$$aMüller, Carina$$b9$$udkfz
000186390 7001_ $$0P:(DE-He78)a5e60710c7515b3e1de74ced6928a9dd$$aSigaud, Romain$$b10$$udkfz
000186390 7001_ $$aEggert, Angelika$$b11
000186390 7001_ $$aSimon, Thorsten$$b12
000186390 7001_ $$aNiehues, Tim$$b13
000186390 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b14$$udkfz
000186390 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian W$$b15$$udkfz
000186390 7001_ $$0P:(DE-He78)a6b5fcabf661bef95109dbee87dc5271$$avan Tilburg, Cornelis M$$b16$$udkfz
000186390 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b17$$udkfz
000186390 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b18$$udkfz
000186390 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b19$$udkfz
000186390 7001_ $$0P:(DE-He78)143af26de9d57bf624771616318aaf7c$$aWitt, Olaf$$b20$$udkfz
000186390 7001_ $$0P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aMilde, Till$$b21$$eLast author$$udkfz
000186390 773__ $$0PERI:(DE-600)1468190-0$$a10.1016/j.ejca.2022.11.015$$gVol. 180, p. 71 - 84$$p71 - 84$$tEuropean journal of cancer$$v180$$x0014-2964$$y2023
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