<i>CREBBP</i> histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory follicular lymphoma
Despite the clinical and molecular heterogeneity of follicular lymphoma (FL), there remains a lack of biomarker-directed therapeutic approaches in routine clinical practice, with the notable exception of the EZH2 inhibitor tazemetostat in EZH2-mutant FL. Here we examined whether gene mutation status predicts response to clinical mTOR inhibitors (mTORi) in FL, by performing targeted mutational profiling of biopsies from 21 relapsed/refractory FL patients treated with mTORi everolimus or temsirolimus within clinical trials. We observed an enrichment of mutations within the catalytic histone acetyltransferase (HAT) domain of CREBBP in mTORi-responders, and describe distinct transcriptional characteristics and co-occurring mutations of FL harbouring these mutations; reinforcing the growing appreciation of CREBBP<sup>HAT</sup> mutation as a key biological determinant and its promise as a therapeutic biomarker in FL.
Authors
- Thomas E. Witzig (ORCID: https://orcid.org/0000-0002-4215-6500)
- Sonali M. Smith (ORCID: https://orcid.org/0000-0002-9893-4949)
- Findlay Bewicke‐Copley (ORCID: https://orcid.org/0000-0003-1292-7965)
- Karina Close (ORCID: https://orcid.org/0009-0003-4237-4617)
- Anne J. Novak (ORCID: https://orcid.org/0000-0002-7904-1651)
- Maria Calaminici
- Koorosh Korfi (ORCID: https://orcid.org/0000-0001-5009-4509)
- Alejo Efeyan (ORCID: https://orcid.org/0000-0002-3806-6799)
- Jessica Okosun (ORCID: https://orcid.org/0000-0001-6021-5044)
- Emil Kumar (ORCID: https://orcid.org/0009-0000-7580-4482)
- Stephen M. Ansell (ORCID: https://orcid.org/0000-0003-1244-6758)
- Michael Richard Green (ORCID: https://orcid.org/0000-0001-6309-9472)
- Michael Leukam (ORCID: https://orcid.org/0000-0002-7342-6649)
- Andrew Clear (ORCID: https://orcid.org/0000-0001-8246-5642)
- Jude Fitzgibbon
- Barrie Peck (ORCID: https://orcid.org/0000-0002-6687-8495)
- James A. Heward (ORCID: https://orcid.org/0000-0002-4022-1532)
- Jun Wang (ORCID: https://orcid.org/0000-0001-9957-9208)
- Jessica Scott
- R. Siebert
Institutions
- Mayo Clinic (US)
- The University of Texas MD Anderson Cancer Center (US)
- Queen Mary University of London (GB)
- Christian-Albrechts-Universität zu Kiel (DE)
- University of Chicago (US)
- Spanish National Cancer Research Centre (ES)
- University Hospital Schleswig-Holstein (DE)
- Centro de Investigación del Cáncer (ES)
- University of Lübeck (DE)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2024-08-26
- DOI
- https://doi.org/10.1111/bjh.19671
- Citations
- 1
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.42
Funders
- Cancer Research UK