The genomic landscape of two Burkitt lymphoma cases and derived cell lines: comparison between primary and relapse samples. Issue 9 (2nd September 2018) - Wever, Claudia M.
Abstract: Relapse occurs in 10–40% of Burkitt lymphoma (BL) patients that have completed intensive chemotherapy regimens and is typically fatal. While treatment-naive BL has been characterized, the genomic landscape of BL at the time of relapse (rBL) has never been reported. Here, we present a genomic characterization of two rBL patients. The diagnostic samples had mutations common in BL, including MYC and CCND3 . Additional mutations were detected at relapse, affecting important pathways such as NFκB ( IKBKB ) and MEK/ERK ( NRAS ) signaling, glutamine metabolism ( SIRT4 ), and RNA processing ( ZFP36L2) . Genes implicated in drug resistance were also mutated at relapse ( TP53, BAX, ALDH3A1, APAF1, FANCI ). This concurrent genomic profiling of samples obtained at diagnosis and relapse has revealed mutations not previously reported in this disease. The patient-derived cell lines will be made available and, along with their detailed genetics, will be a valuable resource to examine the role of specific mutations in therapeutic resistance.