Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

DNA Methylation Profiles Are Stable in H3 K27M-Mutant Diffuse Midline Glioma Neurosphere Cell Lines

Version 1 : Received: 6 March 2024 / Approved: 7 March 2024 / Online: 7 March 2024 (09:17:01 CET)

A peer-reviewed article of this Preprint also exists.

Schniederjan, M.J.; Potnis, C.; Vasudevaraja, V.; Moser, C.D.; Watson, B.; Snuderl, M.; MacDonald, T.; Rogers, B.B. DNA Methylation Profiles Are Stable in H3 K27M-Mutant Diffuse Midline Glioma Neurosphere Cell Lines. Children 2024, 11, 492. Schniederjan, M.J.; Potnis, C.; Vasudevaraja, V.; Moser, C.D.; Watson, B.; Snuderl, M.; MacDonald, T.; Rogers, B.B. DNA Methylation Profiles Are Stable in H3 K27M-Mutant Diffuse Midline Glioma Neurosphere Cell Lines. Children 2024, 11, 492.

Abstract

Diffuse midline gliomas are among the deadliest human cancers and have had little progress in treatment in the last 50 years. Cell cultures of these tumors have been developed recently, but it is unknown the degree to which such cultures retain the characteristics of the source tumors. DNA methylation profiling offers a powerful tool to look at genome-wide epigenetic changes that are biologically meaningful and can help assess the similarity of cultured tumor cells to their in vivo progenitors. Paraffinized diagnostic tissue from three diffuse intrinsic pontine gliomas with H3 K27M mutations was compared with subsequent passages of neurosphere cell cultures from those tumors. Each cell line was passaged 3-4 times and analyzed with DNA methylation arrays and standard algorithms that provided comparison of diagnostic classification and cluster analysis. All samples tested maintained high classifier scores and clustered within the reference group of H3 K27M-mutant diffuse midline gliomas. There was a gain of 1q in all cell lines, with two cell lines initially manifesting the gain of 1q only during culture. In vitro cell cultures of H3 K27M-mutant gliomas maintain high degrees of similarity in DNA methylation profiles to their source tumor, confirming their fidelity even with some chromosomal changes.

Keywords

DNA methylation; H3 K27M; cell culture; diffuse midline glioma; DIPG

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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