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

• Published in: Blood cancer journal (New York) Vol. 9; no. 12; pp. 91 - 10
• Main Authors: Mundo, Lucia, Ambrosio, Maria Raffaella, Raimondi, Francesco, Del Porro, Leonardo, Guazzo, Raffaella, Mancini, Virginia, Granai, Massimo, Jim Rocca, Bruno, Lopez, Cristina, Bens, Susanne, Onyango, Noel, Nyagol, Joshua, Abinya, Nicholas, Navari, Mohsen, Ndede, Isaac, Patel, Kirkita, Paolo Piccaluga, Pier, Bob, Roshanak, de Santi, Maria Margherita, Russell, Robert B., Lazzi, Stefano, Siebert, Reiner, Stein, Harald, Leoncini, Lorenzo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.11.2019; Springer Nature B.V
• Subjects: 631/67/1990; 631/67/1990/291; Adolescent; Adult; Aged; Biomedical and Life Sciences; Biomedicine; Burkitt Lymphoma - epidemiology; Burkitt Lymphoma - genetics; Burkitt Lymphoma - metabolism; Burkitt Lymphoma - pathology; Cancer Research; Child; Female; Gene Expression Regulation, Neoplastic; Genes, myc; Genes, Switch; Genomics - methods; Hematology; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Immunophenotyping; Lymphoma; Male; Middle Aged; Models, Molecular; Mutation; Oncology; Protein Conformation; Protein expression; Proteins; RNA, Messenger - genetics; Structure-Activity Relationship; Translocation, Genetic; Young Adult
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-019-0252-2

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.