Wies R Vallentgoed, Youri Hoogstrate, Karin A van Garderen, Levi van Hijfte, Erik van Dijk, Mathilde C M Kouwenhoven, Johanna M Niers, Kaspar Draaisma, Ivonne Martin, Wendy W J de Leng, C Mircea S Tesileanu, Iris de Heer, Maud Diepeveen, Anna Lavrova, Paul P Eijk, Marcel Bühler, Wolfgang Wick, Paul M Clement, Marc Sanson, Enrico Franceschi, Thierry Gorlia, Vassilis Golfinopoulos, Michael Weller, Tobias Weiss, Pierre A Robe, Johan M Kros, Marion Smits, Mark van de Wiel, Bauke Ylstra, Roel G W Verhaak, Martin J van den Bent, Bart A Westerman, Pieter Wesseling, Pim J French
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引用次数: 0
Abstract
The evolutionary processes that drive malignant progression of IDH-mutant astrocytomas remain unclear. Here, we performed multiomics on matched initial and recurrent tumor samples from a cohort of 105 patients and overlaid the data with detailed clinical annotation. We identified overlapping features associated with malignant progression that are derived from three molecular mechanisms: cell cycling, tumor cell (de)differentiation and remodeling of the extracellular matrix. Together, they provide a rationale of the underlying biology of tumor malignancy. DNA methylation levels decreased over time, predominantly in tumors with malignant transformation, and co-occurred with poor prognostic genetic events. We identified a DNA methylation-based signature strongly associated with survival, which allows objective, molecular-based grading of IDH-mutant astrocytomas to aid clinical decision making. Our findings were validated on large, independent cohorts of IDH-mutant astrocytoma samples. Lastly, in this retrospective study, we found little effect of radiotherapy or chemotherapy on the molecular features associated with malignant progression.
期刊介绍：
Cancer is a devastating disease responsible for millions of deaths worldwide. However, many of these deaths could be prevented with improved prevention and treatment strategies. To achieve this, it is crucial to focus on accurate diagnosis, effective treatment methods, and understanding the socioeconomic factors that influence cancer rates.
Nature Cancer aims to serve as a unique platform for sharing the latest advancements in cancer research across various scientific fields, encompassing life sciences, physical sciences, applied sciences, and social sciences. The journal is particularly interested in fundamental research that enhances our understanding of tumor development and progression, as well as research that translates this knowledge into clinical applications through innovative diagnostic and therapeutic approaches. Additionally, Nature Cancer welcomes clinical studies that inform cancer diagnosis, treatment, and prevention, along with contributions exploring the societal impact of cancer on a global scale.
In addition to publishing original research, Nature Cancer will feature Comments, Reviews, News & Views, Features, and Correspondence that hold significant value for the diverse field of cancer research.
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