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000301546 0247_ $$2doi$$a10.1158/2643-3230.BCD-24-0328
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000301546 1001_ $$00000-0002-8638-9365$$aDiamond, Benjamin$$b0
000301546 245__ $$aMutagenic impact and evolutionary influence of chemo-radiotherapy in hematologic malignancies.
000301546 260__ $$aPhiladelphia, PA$$bAmerican Association for Cancer Research$$c2025
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000301546 520__ $$aIonizing radiotherapy (RT) is a widely used treatment strategy for malignancies. In solid tumors, RT-induced double-strand breaks lead to the accumulation of indels, and their repair by non-homologous end-joining has been linked to the ID8 mutational signature in surviving cells. However, the extent of RT-induced mutagenesis in hematologic malignancies and its impact on their mutational profiles and interplay with commonly used chemotherapies has not yet been explored. Here, we interrogated 580 whole-genome sequence samples (WGS) from patients with large B-cell lymphoma, multiple myeloma, and myeloid neoplasms and identified ID8 only in relapsed disease. Yet, ID8 was detected after exposure to both RT and mutagenic chemotherapy (i.e., platinum and melphalan). Using WGS of single-cell colonies derived from treated lymphoma cells, we revealed a dose-response relationship between RT and platinum and ID8. Finally, using ID8 as a genomic barcode we demonstrate that a single RT-surviving cell may seed distant relapse.
000301546 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000301546 7001_ $$00000-0002-7623-7018$$aChahar, Dhanvantri$$b1
000301546 7001_ $$00000-0002-7789-1257$$aJain, Michael D$$b2
000301546 7001_ $$0P:(DE-He78)b06e4e56845c7f91bd749bb7e6ac9d51$$aPoos, Alexandra$$b3$$eFirst author$$udkfz
000301546 7001_ $$00000-0003-3137-6847$$aDurante, Michael A$$b4
000301546 7001_ $$00000-0002-2746-0053$$aZiccheddu, Bachisio$$b5
000301546 7001_ $$00000-0002-4529-7405$$aKaddoura, Marcella$$b6
000301546 7001_ $$00009-0009-1852-3495$$aPapadimitriou, Marios$$b7
000301546 7001_ $$00000-0001-7873-4854$$aMaclachlan, Kylee H$$b8
000301546 7001_ $$00000-0002-5467-9253$$aJelinek, Tomas$$b9
000301546 7001_ $$00000-0002-3971-2393$$aDavies, Faith E$$b10
000301546 7001_ $$00000-0002-6885-3320$$aFigura, Nicholas B$$b11
000301546 7001_ $$00000-0002-4271-6360$$aMorgan, Gareth J$$b12
000301546 7001_ $$00000-0002-6226-1252$$aMai, Elias K$$b13
000301546 7001_ $$00000-0001-9422-6614$$aWeisel, Katja$$b14
000301546 7001_ $$00000-0001-7594-6288$$aFenk, Roland$$b15
000301546 7001_ $$0P:(DE-He78)1cb537e833afd985097ccfaddffb2ef3$$aRaab, Marc-Steffen$$b16
000301546 7001_ $$00000-0002-5484-8731$$aUsmani, Saad$$b17
000301546 7001_ $$00000-0001-6485-4839$$aLandgren, Ola$$b18
000301546 7001_ $$00000-0001-9063-6691$$aLocke, Frederick L$$b19
000301546 7001_ $$aGoldschmidt, Hartmut$$b20
000301546 7001_ $$00000-0003-1842-228X$$aSchatz, Jonathan Harry$$b21
000301546 7001_ $$0P:(DE-He78)66b39a79f3f922997656d7b902d324fb$$aWeinhold, Niels$$b22$$eLast author$$udkfz
000301546 7001_ $$00000-0002-5017-1620$$aMaura, Francesco$$b23
000301546 773__ $$0PERI:(DE-600)3028898-8$$a10.1158/2643-3230.BCD-24-0328$$n5$$p450-463$$tBlood cancer discovery$$v6$$x2643-3230$$y2025
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