Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.
儿童、青少年和年轻成人（CAYA）中的侵袭性B细胞非霍奇金淋巴瘤（NHL）包括伯基特淋巴瘤（BL）、弥漫性大B细胞淋巴瘤（DLBCL），以及一部分具有这些实体中间特征的高级肿瘤，其遗传和分子特征尚未完全阐明。在本研究中，我们利用靶向下一代测序以及侵袭性淋巴瘤基因表达生发中心B细胞样（GCB）、活化B细胞样（ABC）和暗区特征（DZsig），对37例CAYA中的侵袭性B-NHL进行了表征，其中33例具有高级别形态学，4例为具有MYC重排（MYC-R）的DLBCL。22例肿瘤具有MYC-R而无BCL2断裂，两例MYC非重排病例具有BCL6易位。MYC-R病例，包括DLBCL，携带BL相关突变和拷贝数改变。相反，MYC非重排淋巴瘤在B细胞受体信号/NF-κB通路中发生改变（71%）。DZsig在12/13的MYC-R肿瘤中表达，但仅在2/10的MYC非重排GCB肿瘤中表达（P < 0.001）。整个队列的3年无事件生存期（EFS）为79.6%。TP53和KMT2C突变导致较差预后（3年EFS P < 0.05）。总体而言，CAYA中的MYC-R淋巴瘤具有与BL相似的分子特征，无论其高级别或DLBCL形态学如何；而MYC非重排淋巴瘤具有更异质的遗传改变，更接近DLBCL。
MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma
肿瘤(癌症)患者之家