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April 24th, 2025
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Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
cancer biology
biorxiv

Chromosomal Aneuploidy in Normal, Non-Neuronal Brain Nuclei of Glioblastoma Patients is Not a Cancer Driver

Montagna, C.Open in Google Scholar•Albert, O.Open in Google Scholar•Sun, S.Open in Google Scholar•Lin, J.-R.Open in Google Scholar•Lee, M.Open in Google Scholar•Chan, C.Open in Google Scholar•Maslov, A. Y.Open in Google Scholar•Ellerby, L.Open in Google Scholar•Huttner, A.Open in Google Scholar•Zhang, Z.Open in Google Scholaret al.

Aneuploidy is a hallmark of cancers, including high-grade glioma (GBM), one of the most aggressive brain tumors. To assess whether increased aneuploidy already occurs in normal brain tissue of GBM patients, we performed single-nucleus whole-genome sequencing on 225 non-neuronal cortical nuclei from 12 disease-free individuals and 6 GBM patients, in the latter analyzing both tumor and non-tumor distal regions. Somatic aneuploidy was found in approximately 15% of non-neuronal nuclei in the adult human cortex, with recurrent chromosome 16p aneuploidy in up to 4% of nuclei. In contrast, about 51% of GBM tumor nuclei showed frequent aneuploidy of chromosomes 7 and 10, consistent with known GBM profiles. Notably, non-tumor brain regions from GBM patients exhibited aneuploidy frequencies and patterns similar to controls, including recurrent 16p involvement. These findings indicate that somatic aneuploidy in non-neuronal cells is a normal feature of the adult human brain and not linked to increased GBM risk.

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