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Updated: Jun 15, 2025

Assays for Validating Histone Acetyltransferase Inhibitors
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Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

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CREBBP histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory

Emil Arjun Kumar1, Koorosh Korfi2, Findlay Bewicke-Copley1,2

  • 1Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.

British Journal of Haematology
|August 27, 2024
PubMed

Insights

Researchers investigated gene mutations in follicular lymphoma (FL) to predict response to mTOR inhibitors. CREBBP mutations in the HAT domain were linked to better responses, highlighting their potential as a therapeutic biomarker in FL.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Follicular lymphoma (FL) exhibits significant clinical and molecular heterogeneity.
  • Current treatment strategies lack widespread biomarker-directed approaches, except for EZH2 inhibitors in EZH2-mutant FL.

Purpose of the Study:

  • To determine if gene mutation status predicts response to mammalian target of rapamycin inhibitors (mTORi) in follicular lymphoma.
  • To identify potential therapeutic biomarkers for FL treatment.

Main Methods:

  • Targeted mutational profiling of tumor biopsies from 21 relapsed/refractory FL patients treated with mTORi (everolimus or temsirolimus) in clinical trials.
  • Analysis of gene mutation status in relation to clinical response to mTOR inhibitors.

Main Results:

  • An enrichment of mutations within the catalytic histone acetyltransferase (HAT) domain of CREBBP was observed in patients who responded to mTOR inhibitors.
  • Distinct transcriptional profiles and co-occurring mutations were identified in FL cases with CREBBPHAT mutations.

Conclusions:

  • CREBBPHAT mutations are associated with response to mTOR inhibitors in follicular lymphoma.
  • CREBBPHAT mutation status shows promise as a predictive biomarker for mTOR inhibitor therapy in FL.
Keywords:
CREBBPfollicular lymphomageneticsmTOR inhibitionmutation analysis

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