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Blood Cancer J. 2019 Nov 20;9(12):91. doi: 10.1038/s41408-019-0252-2.

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

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Department of Medical Biotechnology, University of Siena, Siena, Italy.
Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany.
Ulm University and Ulm University Medical Center, Ulm, Germany.
University of Nairobi, Nairobi, Kenya.
Department of Medical Biotechnology & Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Moi Eldoret University, Eldoret, Kenya.
Department of Experimental, Diagnostic, and Specialty Medicine Bologna University Medical School, S. Orsola Malpighi Hospital, Bologna and Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
Pathodiagnostik Lab, Berlin, Germany.
Department of Medical Biotechnology, University of Siena, Siena, Italy.


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.

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