Pediatric B-cell precursor (BCP) lymphoblastic malignancies are neoplasms with manifestation either in the bone marrow or blood (BCP acute lymphoblastic leukemia [BCP-ALL]) or are less common in extramedullary tissue (BCP lymphoblastic lymphoma [BCP-LBL]). Although both presentations are similar in morphology and immunophenotype, molecular studies have been virtually restricted to BCP-ALL so far. The lack of molecular studies on BCP-LBL is due to its rarity and restriction on small, mostly formalin-fixed paraffin-embedded (FFPE) tissues. Here, to our knowledge, we present the first comprehensive mutational and transcriptional analysis of what we consider the largest BCP-LBL cohort described to date (n = 97). Whole-exome sequencing indicated a mutational spectrum of BCP-LBL, strikingly similar to that found in BCP-ALL. However, epigenetic modifiers were more frequently mutated in BCP-LBL, whereas BCP-ALL was more frequently affected by mutation in genes involved in B-cell development. Integrating copy number alterations, somatic mutations, and gene expression by RNA sequencing revealed that virtually all molecular subtypes originally defined in BCP-ALL are present in BCP-LBL, with only 7% of lymphomas that were not assigned to a subtype. Similar to BCP-ALL, the most frequent subtypes of BCP-LBL were high hyperdiploidy and ::. Tyrosine kinase/cytokine receptor rearrangements were detected in 7% of BCP-LBL. These results indicate that genetic subtypes can be identified in BCP-LBL using next-generation sequencing, even in FFPE tissue, and may be relevant to guide treatment.

中文翻译：

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儿童 B 细胞前体淋巴母细胞淋巴瘤的突变和转录情况

儿童 B 细胞前体 (BCP) 淋巴母细胞恶性肿瘤是在骨髓或血液中表现的肿瘤（BCP 急性淋巴细胞白血病 [BCP-ALL]），或者在髓外组织中较少见（BCP 淋巴母细胞淋巴瘤 [BCP-LBL]）。尽管两种表现在形态学和免疫表型上相似，但迄今为止分子研究实际上仅限于 BCP-ALL。缺乏对 BCP-LBL 的分子研究是由于它的稀有性和对小型、大多是福尔马林固定石蜡包埋 (FFPE) 组织的限制。在这里，据我们所知，我们对迄今为止描述的最大的 BCP-LBL 队列 (n = 97) 进行了首次全面的突变和转录分析。全外显子组测序表明 BCP-LBL 的突变谱与 BCP-ALL 中发现的突变谱惊人相似。然而，表观遗传修饰因子在 BCP-LBL 中更频繁地发生突变，而 BCP-ALL 更频繁地受到参与 B 细胞发育的基因突变的影响。通过 RNA 测序整合拷贝数改变、体细胞突变和基因表达表明，实际上 BCP-ALL 中最初定义的所有分子亚型都存在于 BCP-LBL 中，只有 7% 的淋巴瘤未分配到亚型。与 BCP-ALL 类似，BCP-LBL 最常见的亚型是高超二倍体和 ::。在 7% 的 BCP-LBL 中检测到酪氨酸激酶/细胞因子受体重排。这些结果表明，即使在 FFPE 组织中，也可以使用下一代测序来识别 BCP-LBL 中的遗传亚型，并且可能与指导治疗相关。