Abstract
AbstractMYC 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.
Publisher
Springer Science and Business Media LLC
Reference48 articles.
1. Dang, C. V. MYC on the path to cancer. Cell 149, 22–35 (2012).
2. Ambrosio, M. R. et al. MYC protein expression scoring and its impact on the prognosis of aggressive B-cell lymphoma patients. Haematologica 104, e25–e28 (2019).
3. Sewastianik, T., Prochorec-Sobieszek, M., Chapuy, B. & Juszczyński, P. MYC deregulation in lymphoid tumors: molecular mechanisms, clinical consequences and therapeutic implications. Biochim. Biophys. Acta 1846, 457–467 (2014).
4. Kieffer-Kwon, K. R. et al. Myc regulates chromatin decompaction and nuclear architecture during B cell activation. Mol Cell 67, 566–578 (2017).
5. Beltran, H. The N-myc oncogene: maximizing its targets, regulation, and therapeutic potential. Mol Cancer Res. 12, 815–822 (2014).
Cited by
19 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献