Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198-3135, USA.
Blood. 2012 Apr 19;119(16):3757-66. doi: 10.1182/blood-2011-05-349662. Epub 2012 Feb 28.
Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B-cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are treated similarly in children and both entities have superior outcomes in children compared with adults. Gene expression profiling (GEP) and miRNA expression profiling clearly differentiated pediatric DLBCL from BL, forming distinct clusters regardless of patient age. However, pathway analysis of GEP data identified minor differences between corresponding pediatric and adult tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B-cell subtype was found among pediatric DLBCL. Two cases were molecularly classified as primary mediastinal B-cell lymphoma. We observed frequent abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangement in 31% (5 of 16) and gain or amplification in 50% (6 of 12) nonrearranged cases. MYC rearrangement was present in 96% (23 of 24) BL cases. Array-based CGH analysis identified abnormalities that are shared between adult and pediatric DLBCL (+12q15, +19q13, -6q), and abnormalities unique to the pediatric cases (-4p14, -19q13.32, +16p11.2), suggesting distinct pathogenetic mechanisms relative to age. Elucidation of the underlying target genes may provide insight into factors that modulate outcome and could provide potential novel therapeutic targets with less toxicity for pediatric patients with B-cell non-Hodgkin lymphoma.
伯基特淋巴瘤（BL）多见于儿童患者，而弥漫性大 B 细胞淋巴瘤（DLBCL）则不常见。与成人不同，儿童 BL 和 DLBCL 的治疗方法相似，与成人相比，这两种疾病在儿童中的预后都更好。基因表达谱（GEP）和 miRNA 表达谱清楚地区分了儿童 DLBCL 和 BL，无论患者年龄如何，均形成了不同的聚类。然而，GEP 数据的通路分析发现，相应的儿童和成人肿瘤之间存在微小差异。儿童 DLBCL 中，生发中心 B 细胞亚型占主导地位（6:1），而激活的 B 细胞亚型则较少见。有两例被分子分类为原发性纵隔 B 细胞淋巴瘤。我们观察到儿童 DLBCL 中 8q24 频繁出现异常，包括 31%（16 例中的 5 例）存在 MYC 重排和 50%（12 例非重排病例中的 6 例）存在增益或扩增。96%（23 例中的 24 例）BL 病例存在 MYC 重排。基于阵列的 CGH 分析确定了成人和儿童 DLBCL 之间共有的异常（+12q15、+19q13、-6q），以及儿科病例特有的异常（-4p14、-19q13.32、+16p11.2），这表明与年龄相关的发病机制不同。阐明潜在的靶基因可能有助于深入了解调节预后的因素，并为儿科 B 细胞非霍奇金淋巴瘤患者提供毒性较小的潜在新的治疗靶点。
