Targeted Sequencing of FL patients
Despite the clinical and molecular heterogeneity of follicular lymphoma (FL), tThere remains no a lack of biomarker-directed therapeutic approaches in routine clinical practice,  in follicular lymphoma (FL), highlighting the paucity of studies in this area.with the notable exception of EZH2 inhibitor Tazemetostat in EZH2-mutant FL. Here weWe examined whether gene mutation status predicts response to clinical mTOR inhibitors (mTORi) in FL, by performing targeted mutational profiling of 21 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 CREBBPHAT mutation as a key biological determinant and its promise as a therapeutic biomarker in FL.
Despite the clinical and molecular heterogeneity of follicular lymphoma (FL), tThere remains no a lack of biomarker-directed therapeutic approaches in routine clinical practice,  in follicular lymphoma (FL), highlighting the paucity of studies in this area.with the notable exception of EZH2 inhibitor Tazemetostat in EZH2-mutant FL. Here weWe examined whether gene mutation status predicts response to clinical mTOR inhibitors (mTORi) in FL, by performing targeted mutational profiling of 21 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 CREBBPHAT mutation as a key biological determinant and its promise as a therapeutic biomarker in FL.
Barts Cancer Institute