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

Abstract

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.

Integrating genetic dependencies and genomic alterations across pathways and cancer types

“…MYCN is highly expressed in a subset of tissue including forebrain and hindbrain whereas MYC expression is ubiquitous [114]. Previous studies have suggested that MYCN and MYC may be redundant, and that MYCN can compensate MYC activity [114,115]. In fact, we observe that MYC expression is high across most cancer types in the dataset, with neuroblastoma a prominent exception; at the same time, MYCN expression is low across most cancer types except for neuroblastoma ( Fig.…”

Clinical Interest of LMO2 Testing for the Diagnosis of Aggressive Large B-Cell Lymphomas

“…Some studies showed that MYC mutations are common in BL and mainly locate in the first 100 aa of the MYC protein. This is the region recognized by MYC clone Y69, and this may explain the absence of MYC protein expression in such cases [30]. Moreover, recent studies suggest that LMO2 also appears to be useful for the differential diagnosis of BL and the provisional category of Burkitt-like lymphoma with 11q aberration.…”

Linfoma de Burkitt nasofaríngeo

“…Sin embargo, la dificultad para la realización de pruebas moleculares hace que la histología e inmunohistoquímica sean suficientes para el diagnóstico. [7][8][9] En los auxiliares laboratoriales destacan la elevación de la deshidrogenasa láctica (50%) y del ácido úrico (25%) pero son inespecíficos. Las técnicas de imagen son de utilidad para sospecha diagnóstica, localización exacta, realización de biopsia y control terapéutico.…”

“…Las técnicas de imagen son de utilidad para sospecha diagnóstica, localización exacta, realización de biopsia y control terapéutico. [7][8][9] Existe poca bibliografía con casos similares; sin embargo, en las publicaciones previas se resalta la importancia de la sintomatología asociada a la localización anatómica, como la afección rinosinusal y los cambios en fonación y ronquidos. También hay síntomas neurológicos que coinciden, principalmente la parálisis facial.…”

“…El linfoma de Burkitt fue descubierto a principios del siglo XX, siendo Denis Burkitt en 1958 quien proporcionó la descripción detallada de esta patología; además, fue el primer tumor asociado a etiología viral y en demostrarse una translocación cromosómica activadora del oncogén. [5][6][7] Se origina por una proliferación clonal de las células tipo B del centro germinal ocasionado principalmente por la translocación t (8,14), la cual está presente en la mayoría de este tipo de linfomas. [7][8][9] Fuera de África existe poca literatura acerca de la presentación de linfomas de Burkitt en la nasofaringe.…”