Somatic mutations of the CREBBP and EP300 genes affect response to histone deacetylase inhibition in malignant DLBCL clones

Christen Lykkegaard Andersen; Fazila Asmar; Tobias Klausen; Hans Hasselbalch; Kirsten Grønbæk

doi:10.1016/j.lrr.2012.10.002

Somatic mutations of the CREBBP and EP300 genes affect response to histone deacetylase inhibition in malignant DLBCL clones

Leuk Res Rep. 2012 Dec 8;2(1):1-3. doi: 10.1016/j.lrr.2012.10.002. eCollection 2012.

Authors

Christen Lykkegaard Andersen¹, Fazila Asmar², Tobias Klausen³, Hans Hasselbalch⁴, Kirsten Grønbæk²

Affiliations

¹ Department of Hematology, Roskilde University Hospital, Denmark ; Department of Hematology, Copenhagen University Hospital, Denmark.
² Department of Hematology, Copenhagen University Hospital, Denmark.
³ Department of Hematology, Herlev University Hospital, Denmark.
⁴ Department of Hematology, Roskilde University Hospital, Denmark.

Abstract

Heterogeneous clinical responses to histone deacetylase inhibitors (HDACi) in diffuse large B-cell lymphoma (DLBCL) have prompted a need for evaluating the impact of mutations in the histone acetyl transferases (HAT) CREBBP and EP300 on HDACi treatment outcome. We identified four DLBCL cell lines; Toledo, with mutations in CREBBP and EP300, SUDHL-7 with mutation of CREBBP and wild-type (wt) EP300, RL with mutation of EP300 and wt CREBBP, and U2932 with wt CREBBP and wt EP300. Vorinostat treatment induced apoptosis significantly more rapid and profound in the CREBBP/EP300 double mutant cell line. Our results suggest that pre-treatment stratification according to HAT defects may be relevant in DLBCL.

Keywords: Diffuse large B-cell lymphoma; Histone acetyl transferase; Histone deacetylase inhibition; Somatic mutation; Vorinostat.