CDKN2A deletion and radiation sensitivity in IDH-mutant astrocytomas.

• DOI: 10.1200/jco.2024.42.16_suppl.2041
• Publication Date: 2024-06-18T20:56:33Z
• Authors: Logan Muzyka; Yosuke Kitagawa; Ali Mohamed Nasser; Ethan A Wetzel; Julie J. Miller; Hiroaki Wakimoto; Daniel P. Cahill
• Keywords: Radiation sensitivity

2041 Background: IDH-mutant astrocytomas represent the most prevalent primary tumors in younger adults (<45yo). A substantial minority of these exhibit deletion CDKN2A (Cyclin-Dependent Kinase Inhibitor Gene 2A). Homozygous this gene– which encodes tumor suppressor protein p16 – is associated with a malignant phenotype and poorer prognosis astrocytoma. deletions are primarily observed that have received radiation therapy (RT), suggesting potential mechanistic relationship between RT deletion. This observation gives rise to two alternative hypotheses: either causing DNA damage irradiated cells, leading induction subclonal deletion, or subset cells already possesses resistant RT, resulting treatment selecting for subsequent emergence cells. Here, we sought ascertain influence on astrocytoma cellular response RT. Methods: The antitumor effect was evaluated vitro using patient-derived MGG152. homozygous engineered parental line, creating paired line permit an isogenic comparison intact versus deleted photon irradiator used deliver range clinically-relevant doses spanning from 0 20 gray (Gy). Differences cell viability after predetermined incubation period were examined relevant statistical comparisons performed. Results: Dose-response curves therapy, comparing lines, generated (Table). Both lines exhibited significant reductions following exposure at above 2Gy (p < 0.001). CDKN2A-deleted displayed small but significantly greater sensitivity than CDKN2A-intact 1, 2, 5Gy Conclusions: Our findings offer evidence indicating loss does not bestow radioresistance astrocytomas. These align hypothesis radiotherapy (RT) might promote damage, consequently, tumors. [Table: see text]