德国海德堡大学Niels Weinhold研究组取得一项新突破。他们探明了时间基因组动力学塑造多发性骨髓瘤的临床轨迹。该研究于2025年8月20日发表于国际一流学术期刊《自然—遗传学》杂志上。

为了揭示这一时间轴及其对临床结果的影响，该课题组研究人员分析了来自382名患者的421个全基因组序列。利用类似时钟的突变特征，研究团队估计在事件发生和诊断之间有20到40年的时间滞后。该课题组研究人员证明，高二倍体患者的奇数染色体三体可以与其他染色体获得（例如1q获得）同时获得。该研究团队发现，当免疫球蛋白重链易位同时发生时，高二倍体是在免疫球蛋白重链易位后获得的。最后，早期1q增加的患者与1q扩增的患者有相似的不良结果（>1额外拷贝），但比晚期1q增加的患者更糟糕。这一发现强调，1q增益的预后影响更多地取决于获取的时间，而不是获得的拷贝数。总的来说，这项研究有助于更好地了解骨髓瘤的生活史，并可能具有预后意义。

据悉，多发性骨髓瘤进化的特点是基因组驱动因素随时间的积累。

附：英文原文

Title: Temporal genomic dynamics shape clinical trajectory in multiple myeloma

Author: Maura, Francesco, Kaddoura, Marcella, Poos, Alexandra M., Baughn, Linda B., Ziccheddu, Bachisio, Brtsch, Marc-Andrea, Cirrincione, Anthony, Maclachlan, Kylee, Chojnacka, Monika, Diamond, Benjamin, Papadimitriou, Marios, Blaney, Patrick, John, Lukas, Reichert, Philipp, Huhn, Stefanie, Gagler, Dylan, Zhang, Yanming, Dogan, Ahmet, Lesokhin, Alexander M., Davies, Faith, Goldschmidt, Hartmut, Fenk, Roland, Weisel, Katja C., Mai, Elias K., Korde, Neha, Morgan, Gareth J., Rajkumar, S. Vincent, Kumar, Shaji, Usmani, Saad, Landgren, Ola, Raab, Marc S., Weinhold, Niels

Issue&Volume: 2025-08-20

Abstract: 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.

DOI: 10.1038/s41588-025-02292-1

Source: https://www.nature.com/articles/s41588-025-02292-1