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Impact of CDKN2A/B, MTAP, and TERT Genetic Alterations on Survival in IDH Wild Type Glioblastomas. | LitMetric

AI Article Synopsis

  • Poor outcomes in IDH wild-type glioblastomas highlight the need to identify genetic alterations that can indicate poor survival and guide personalized treatment options for patients.
  • A study reviewed genetic data from 167 patients with IDHwt glioblastomas and found that deletions in CDKN2A, CDKN2B, and MTAP are predictors of worse overall survival, independent of other factors.
  • Additionally, TERT mutations and CDKN2A copy loss showed significant negative associations with overall survival when patients received lower radiation doses, suggesting these genetic markers could help tailor treatment approaches.

Article Abstract

Purpose: Poor outcomes in IDH wild-type (IDHwt) glioblastomas indicate the need to determine which genetic alterations can indicate poor survival and guidance of patient specific treatment options. We sought to identify the genetic alterations in these patients that predict for survival when adjusting particularly for treatments and other genetic alterations.

Methods: A cohort of 167 patients with pathologically confirmed IDHwt glioblastomas treated at our institution was retrospectively reviewed. Next generation sequencing was performed for each patient to determine tumor genetic alterations. Multivariable cox proportional hazards analysis for overall survival (OS) was performed to control for patient variables.

Results: CDKN2A, CDKN2B, and MTAP deletion predict for worse OS independently of other genetic alterations and patient characteristics (hazard ratio [HR] 2.192, p = 0.0017). Patients with CDKN2A copy loss (HR 2.963, p = 0.0037) or TERT mutated (HR 2.815, p = 0.0008) glioblastomas exhibited significant associations between radiation dose and OS, while CDKN2A and TERT wild type patients did not. CDKN2A deleted patients with NF1 mutations had worse OS (HR 1.990, p = 0.0540), while CDKN2A wild type patients had improved OS (HR 0.229, p = 0.0723). Patients with TERT mutated glioblastomas who were treated with radiation doses < 45 Gy (HR 3.019, p = 0.0010) but not those treated with ≥ 45 Gy exhibited worse OS compared to those without TERT mutations.

Conclusion: In IDHwt glioblastomas, CDKN2A, CDKN2B, and MTAP predict for poor prognosis. TERT and CDKN2A mutations are associated with worse survival only when treated with lower radiation doses, thus potentially providing a genetic marker that can inform clinicians on proper dose-fractionation schemes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666584PMC
http://dx.doi.org/10.1007/s12672-022-00590-2DOI Listing

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