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Loss of CDKN2A/B is a Hallmark of RTK II Glioblastomas

Year: 2025

Type: article

Abstract: Glioblastomas represent the most prevalent primary brain tumors in adults.Due to their highly malignant biological behavior, they are classified as grade 4 according to the World Health Organization (WHO) classification of brain tumors.Despite the progress in understanding the molecular pathogenesis of these tumors, no curative therapy has been developed for patients with glioblastoma.In this study, an integrated comparative analysis of cyclin-dependent kinase inhibitor (CDKN) 2A/B chromosomal deletion was performed on 45 glioblastomas, representing the most frequent molecular subtypes of glioblastomas, receptor tyrosine kinase (RTK) I (n=13), RTK II (n=15), and the mesenchymal subtype (MES) (n=17).The analysis of copy number variation (CNV) profiles was conducted on CDKN2A/B losses.Subsequent statistical analysis was then applied to correlate the collected data with molecular glioblastoma epigenotypes.Loss of CDKN2A/B was found 44% (20/45) of all glioblastomas, thereby, in 46% (6/13) of RTK I, 67% (10/15) RTK II, and 24% (4/17) of MES.Statistical analysis showed that loss of CDKN2A/B is significant (p < 0.01) in RTK II compared with MES.Even though CDKN2A/B does not per se function as a molecular target, there is great potential for enhancing treatment outcomes through the restoration of the tumor-suppressing capabilities of CDKN2A/B.This strategy can be employed in therapeutic interventions and is a promising avenue for research.This efficacy of this approach demonstrates high potential, as evidenced by its efficacy in other tumors, including melanoma.

Source: Journal of Cancer

DOI: 10.7150/jca.122609