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Updated: Nov 3, 2025

Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration
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Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration

Published on: December 27, 2024

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Downregulation of ATM and BRCA1 Predicts Poor Outcome in Head and Neck Cancer: Implications for ATM-Targeted Therapy

Yu-Chu Wang1, Ka-Wo Lee2, Yi-Shan Tsai1,3

  • 1Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Journal of Personalized Medicine
|June 2, 2021
PubMed

Insights

Low expression of DNA repair genes ATM and BRCA1 indicates poor prognosis in head and neck cancer (HNC). Betel quid use suppresses these genes, suggesting ATM-targeted therapy may improve outcomes.

Area of Science:

  • Molecular biology
  • Genetics
  • Cancer research

Background:

  • ATM and BRCA1 are crucial DNA repair genes involved in homologous recombination.
  • Altered expression of ATM and BRCA1 is linked to cancer development and treatment response.
  • The prognostic significance of ATM and BRCA1 in head and neck cancer (HNC) remains unclear.

Purpose of the Study:

  • To investigate the prognostic role of ATM and BRCA1 gene expression in HNC.
  • To explore the impact of betel quid (BQ) exposure on ATM and BRCA1 expression in HNC.
  • To evaluate the potential of ATM-targeted therapy in HNC.

Main Methods:

  • Analysis of ATM and BRCA1 expression in two HNC cohorts with and without BQ exposure.
  • Correlation of gene expression with overall survival (OS) using multivariate analysis.
  • Transcriptomic analysis to assess the effect of ATM kinase inhibition.

Main Results:

  • ATM and BRCA1 expression were downregulated in BQ-associated HNC, with arecoline identified as a suppressive agent.
  • Low expression of ATM or BRCA1 independently predicted poor OS in HNC patients.
  • Combined low expression of ATM and BRCA1 significantly worsened OS prediction.
  • ATM kinase inhibition induced apoptosis and enhanced cisplatin cytotoxicity.

Conclusions:

  • Downregulation of ATM and BRCA1 expression is associated with poor prognosis in HNC, particularly in BQ-exposed individuals.
  • ATM and BRCA1 expression levels serve as independent prognostic factors for OS in HNC.
  • Targeting ATM may represent a promising therapeutic strategy for HNC patients with low ATM/BRCA1 expression.
Keywords:
ATMBRCA1KU55933betel quidbiomarkerhead and neck cancerprognosis

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