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000303964 1001_ $$00000-0002-5017-1620$$aMaura, Francesco$$b0
000303964 245__ $$aTemporal genomic dynamics shape clinical trajectory in multiple myeloma.
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000303964 520__ $$aMultiple myeloma evolution is characterized by the accumulation of genomic drivers over time. To unravel this timeline and its impact on clinical outcomes, we analyzed 421 whole-genome sequences from 382 patients. Using clock-like mutational signatures, we estimated a time lag of two to four decades between the initiation of events and diagnosis. We demonstrate that odd-numbered chromosome trisomies in patients with hyperdiploidy can be acquired simultaneously with other chromosomal gains (for example, 1q gain). We show that hyperdiploidy is acquired after immunoglobulin heavy chain translocation when both events co-occur. Finally, patients with early 1q gain had adverse outcomes similar to those with 1q amplification (>1 extra copy), but fared worse than those with late 1q gain. This finding underscores that the 1q gain prognostic impact depends more on the timing of acquisition than on the number of copies gained. Overall, this study contributes to a better understanding of the life history of myeloma and may have prognostic implications.
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000303964 7001_ $$00000-0002-4529-7405$$aKaddoura, Marcella$$b1
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000303964 7001_ $$00000-0001-5229-4897$$aBaughn, Linda B$$b3
000303964 7001_ $$aZiccheddu, Bachisio$$b4
000303964 7001_ $$0P:(DE-He78)8377b61f1b96062008419d3630da31bb$$aBärtsch, Marc-Andrea$$b5$$udkfz
000303964 7001_ $$00000-0002-8133-9158$$aCirrincione, Anthony$$b6
000303964 7001_ $$00000-0001-7873-4854$$aMaclachlan, Kylee$$b7
000303964 7001_ $$aChojnacka, Monika$$b8
000303964 7001_ $$00000-0002-8638-9365$$aDiamond, Benjamin$$b9
000303964 7001_ $$aPapadimitriou, Marios$$b10
000303964 7001_ $$00000-0002-9319-8866$$aBlaney, Patrick$$b11
000303964 7001_ $$0P:(DE-He78)2ffc015bc2bdd9ed7a54d29dc063ab75$$aJohn, Lukas$$b12$$udkfz
000303964 7001_ $$aReichert, Philipp$$b13
000303964 7001_ $$aHuhn, Stefanie$$b14
000303964 7001_ $$aGagler, Dylan$$b15
000303964 7001_ $$aZhang, Yanming$$b16
000303964 7001_ $$00000-0001-6576-5256$$aDogan, Ahmet$$b17
000303964 7001_ $$00000-0001-9321-702X$$aLesokhin, Alexander M$$b18
000303964 7001_ $$aDavies, Faith$$b19
000303964 7001_ $$aGoldschmidt, Hartmut$$b20
000303964 7001_ $$aFenk, Roland$$b21
000303964 7001_ $$aWeisel, Katja C$$b22
000303964 7001_ $$00000-0002-6226-1252$$aMai, Elias K$$b23
000303964 7001_ $$aKorde, Neha$$b24
000303964 7001_ $$00000-0002-4271-6360$$aMorgan, Gareth J$$b25
000303964 7001_ $$aRajkumar, S Vincent$$b26
000303964 7001_ $$00000-0001-5392-9284$$aKumar, Shaji$$b27
000303964 7001_ $$00000-0002-5484-8731$$aUsmani, Saad$$b28
000303964 7001_ $$00000-0001-6485-4839$$aLandgren, Ola$$b29
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000303964 7001_ $$0P:(DE-He78)66b39a79f3f922997656d7b902d324fb$$aWeinhold, Niels$$b31$$eLast author$$udkfz
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