The Effect of NOP16 Mutation in Chronic Lymphocytic Leukemia

NOP16 was the third most important mutation (6.84%) in a reduced-size cohort of 117 patients with Chronic Lymphocytic Leukemia (CLL) whose most recurrent mutations were NOTCH1 (9.4%) and SF3B1 (8.55%). In this paper we analyzed the effect of the NOP16 mutation in gene expression. The NOP16 mutation was predicted with 100% accuracy using a small-scale signature formed by the 26 genes with the highest Fisher’s Ratio. SLC39A4 (ZIP4) and WARS are the most discriminatory genes of this mutation providing a predictive accuracy of 97.4%. The Fold Change analysis also confirmed a very important role of the light (IGKV3D-11, IGKC and IGLJ3) and heavy (IGHG1) chain immunoglobulins, SOX11, CCND1 and CHL1. This analysis also highlights the importance of several mechanisms such as the ZIP4-related apoptosis, the SOX11-CCND1 over expression relationship observed in mantle cell-lymphoma, and CHL1 down regulation and over expression of the midkine-neurite growth-promoting factor that enhances the angiogenic and proliferative activities of cancer cells in different types of solid cancers. Besides, the holdout stability analysis has shown the importance of Signaling Events of B Cell Receptor (BCR), P53 signaling, Infectious disease, and TGF-beta Receptor Signaling. The integration of the NOP16 mutation with the IgHV, NOTCH1 and SF3B1 mutations, that were previously analyzed, confirmed that these mutations only share two high discriminatory genes: IGHG1 and RGS13. These genes are involved in different mechanisms concerning signaling and the immunological system. This analysis opens novel working hypothesis for CLL treatment and prognosis. poor prognosis. Disease progression has also been associated with a number of genetic alterations that include cytogenetic abnormalities and specific gene mutations [14-18]. Besides, aberrant methylation has been described for genes that are specifically deregulated in CLL [19]. Due to their low percentage of occurrence (no higher than 10%) in comparison to their mutational IgHV status (around 60/40%), these studies have shown that any of the individual mutations in CLL patients cannot explain alone the difference in prognosis observed in the CLL patients. Therefore, the main CLL mutations should share some common mechanisms that are responsible for CLL development and bad prognosis. A retrospective analysis to understand the effect the main mutations (IgHV, NOTCH1 and SF3B1) in gene expression and the existing relationships between them have been recently performed using the same dataset [20]. Following the same methodology, we analyze the effect of the NOP16 mutation in gene expression, highlighting the importance of different mechanisms involved in CLL, such as the ZIP4-related apoptosis, the SOX11-CCND1 over expression relationship also observed in mantle cell-lymphoma, and the CHL1 down regulation and over expression of the midkine-neurite growth-promoting factor observed in different types of solid cancers. Besides, the holdout stability analysis has shown the importance of Signaling Events of B Cell Receptor (BCR), P53 signaling, Infectious disease, and TGF-beta Receptor Signaling. Citation: Fernández-Martínez JL, DeAndrés-Galiana EJ, Cernea A (2017) The Effect of NOP16 Mutation in Chronic Lymphocytic Leukemia. J Mol Genet Med 11: 295 doi:10.4172/1747-0862.1000295 Volume 11 • Issue 4 • 1000295 J Mol Genet Med, an open access journal ISSN: 1747-0862 Page 2 of 8 The NOP16 mutation has not been studied before in CLL or in other hematologic malignancies. The current literature concerning NOP16 expression is largely focused in breast cancer, since the expression of this gene induced by estrogens and Myc protein is a marker of poor patient survival [21]. Our expectation is that the knowledge issued from the analysis of the effect of the NOP16 mutation in this reduced cohort where expression data and mutational status of the patients are available, will contribute in the near future to improve CLL treatment and prognosis, with the investigation of novel hypotheses and target therapies issued from this analysis. Particularly, this analysis has confirmed our previous findings concerning the effect of these mutations in the immunological system. We believe that a whole integration of the main mutations and genomic aberrations observed in CLL is needed to find a medical solution to this heterogeneous disease, and constitutes the subject of future research. Materials and Methods