Wever Claudia M, Geoffrion Dominique, Grande Bruno M, Yu Stephen, Alcaide Miguel, Lemaire Maryse, Riazalhosseini Yasser, Hébert Josée, Gavino Christina, Vinh Donald C, Petrogiannis-Haliotis Tina, Dmitrienko Svetlana, Mann Koren K, Morin Ryan D, Johnson Nathalie A
a Department of Medicine , McGill University, Lady Davis Institute, Jewish General Hospital , Montreal , Canada.
b Lady Davis Institute, Jewish General Hospital , Montreal , Canada.
Leuk Lymphoma. 2018 Sep;59(9):2159-2174. doi: 10.1080/10428194.2017.1413186. Epub 2018 Jan 3.
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.
在完成强化化疗方案的伯基特淋巴瘤（BL）患者中，10%-40%会出现复发，且通常是致命的。虽然未经治疗的BL已有特征描述，但复发时BL（rBL）的基因组格局从未被报道过。在此，我们展示了两名rBL患者的基因组特征。诊断样本具有BL中常见的突变，包括MYC和CCND3。复发时检测到其他突变，影响重要通路，如NFκB（IKBKB）和MEK/ERK（NRAS）信号传导、谷氨酰胺代谢（SIRT4）以及RNA加工（ZFP36L2）。与耐药相关的基因在复发时也发生了突变（TP53、BAX、ALDH3A1、APAF1、FANCI）。对诊断和复发时获取的样本进行的这种同步基因组分析揭示了该疾病先前未报道的突变。将提供患者来源的细胞系，连同其详细遗传学信息，将成为研究特定突变在治疗耐药中作用的宝贵资源。
