TY  - JOUR
AU  - Maura, Francesco
AU  - Kaddoura, Marcella
AU  - Poos, Alexandra
AU  - Baughn, Linda B
AU  - Ziccheddu, Bachisio
AU  - Bärtsch, Marc-Andrea
AU  - Cirrincione, Anthony
AU  - Maclachlan, Kylee
AU  - Chojnacka, Monika
AU  - Diamond, Benjamin
AU  - Papadimitriou, Marios
AU  - Blaney, Patrick
AU  - John, Lukas
AU  - Reichert, Philipp
AU  - Huhn, Stefanie
AU  - Gagler, Dylan
AU  - Zhang, Yanming
AU  - Dogan, Ahmet
AU  - Lesokhin, Alexander M
AU  - Davies, Faith
AU  - Goldschmidt, Hartmut
AU  - Fenk, Roland
AU  - Weisel, Katja C
AU  - Mai, Elias K
AU  - Korde, Neha
AU  - Morgan, Gareth J
AU  - Rajkumar, S Vincent
AU  - Kumar, Shaji
AU  - Usmani, Saad
AU  - Landgren, Ola
AU  - Raab, Marc-Steffen
AU  - Weinhold, Niels
TI  - Temporal genomic dynamics shape clinical trajectory in multiple myeloma.
JO  - Nature genetics
VL  - nn
SN  - 1061-4036
CY  - London
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DKFZ-2025-01733
SP  - nn
PY  - 2025
N1  - #EA:A360#LA:A360# / epub
AB  - Multiple 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40835892
DO  - DOI:10.1038/s41588-025-02292-1
UR  - https://inrepo02.dkfz.de/record/303964
ER  -