Oelschläger Lorenz, Künstner Axel, Frey Friederike, Leitner Theo, Leypoldt Lisa, Reimer Niklas, Gebauer Niklas, Bastian Lorenz, Weisel Katja, Sailer Verena-Wilbeth, Röcken Christoph, Klapper Wolfram, Konukiewitz Björn, Murga Penas Eva Maria, Forster Michael, Schub Natalie, Ahmed Helal M M, Kirfel Jutta, von Bubnoff Nikolas Christian Cornelius, Busch Hauke, Khandanpour Cyrus
Department of Hematology and Oncology, University Medical Center Schleswig-Holstein (UKSH), University Cancer Center Schleswig-Holstein (UCCSH), Campus Lübeck, 23538 Lübeck, Germany.
Medical Systems Biology Group, Lübeck Institute of Experimental Dermatology, University of Lübeck, 23538 Lübeck, Germany.
Int J Mol Sci. 2024 Dec 14;25(24):13418. doi: 10.3390/ijms252413418.
The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM. In this study, we analyzed WES data from 35 MM patients to identify potential mutational signatures and driver mutations correlated with clinical and cytogenetic characteristics. Our findings confirm the complex mutational spectrum and its impact on previously described ontogenetic and epigenetic pathways. They show TYW1 as a possible new potential driver gene and find no significant associations of mutational signatures with clinical findings. Further studies are needed to strengthen the role of mutational signatures in the clinical context of patients with MM to improve patient management.
多发性骨髓瘤（MM）复杂且异质性的基因组格局及其许多临床和预后意义仍有待了解。在其他癌症中，如乳腺癌，在临床实践中使用全外显子组测序（WES）和分子特征已经彻底改变了分类、预后预测和患者管理。然而，这种整合在MM中仍处于早期阶段。在本研究中，我们分析了35例MM患者的WES数据，以识别与临床和细胞遗传学特征相关的潜在突变特征和驱动突变。我们的研究结果证实了复杂的突变谱及其对先前描述的个体发生和表观遗传途径的影响。它们显示TYW1可能是一个新的潜在驱动基因，并且未发现突变特征与临床发现之间存在显著关联。需要进一步的研究来加强突变特征在MM患者临床背景中的作用，以改善患者管理。
