文章：

MYC蛋白阴性的伯基特淋巴瘤中，MYC向MYCN表达的分子转换

Molecular switch from MYC to MYCN expression in MYC protein negative Burkitt lymphoma cases

原文发布日期：2019-11-20

DOI: 10.1038/s41408-019-0252-2

类型: Article

开放获取: 是

英文摘要：

MYC is the most altered oncogene in human cancer, and belongs to a large family of genes, including MYCN and MYCL. Recently, while assessing the degree of correlation between MYC gene rearrangement and MYC protein expression in aggressive B-cell lymphomas, we observed few Burkitt lymphoma (BL) cases lacking MYC protein expression despite the translocation involving the MYC gene. Therefore, in the present study we aimed to better characterize such cases. Our results identified two sub-groups of MYC protein negative BL: one lacking detectable MYC protein expression but presenting MYCN mRNA and protein expression; the second characterized by the lack of both MYC and MYCN proteins but showing MYC mRNA. Interestingly, the two sub-groups presented a different pattern of SNVs affecting MYC gene family members that may induce the switch from MYC to MYCN. Particulary, MYCN-expressing cases show MYCN SNVs at interaction interface that stabilize the protein associated with loss-of-function of MYC. This finding highlights MYCN as a reliable diagnostic marker in such cases. Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.
 

摘要翻译： 

MYC是人类癌症中最常改变的癌基因，属于一个大的基因家族，包括MYCN和MYCL。最近，在评估侵袭性B细胞淋巴瘤中MYC基因重排与MYC蛋白表达的相关程度时，我们观察到一些Burkitt淋巴瘤（BL）案例尽管涉及MYC基因的易位，但缺乏MYC蛋白表达。因此，在本研究中，我们旨在更好地描述这些案例。我们的结果确定了两个亚组的MYC蛋白阴性BL：一个缺乏可检测的MYC蛋白表达但呈现MYCN mRNA和蛋白表达；第二个特征为缺乏MYC和MYCN蛋白但显示MYC mRNA。有趣的是，这两个亚组呈现出影响MYC基因家族成员的单核苷酸变异（SNVs）的不同模式，可能诱导从MYC到MYCN的转换。特别是，表达MYCN的案例显示MYCN SNVs在相互作用界面，稳定了与MYC功能丧失相关的蛋白。这一发现突显了MYCN在这些案例中作为可靠的诊断标记。然而，由于两个亚组在临床、形态学和免疫组织化学（除了MYC与MYCN蛋白表达）方面重叠，根据世界卫生组织的当前标准，所描述的案例代表了真正的BL。

原文链接：

Molecular switch from MYC to MYCN expression in MYC protein negative Burkitt lymphoma cases