Brd4::Nutm1 fusion gene initiates NUT carcinoma in vivo.

NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a BRD4::NUTM1 fusion gene. Because the BRD4::NUTM1 gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the Brd4::Nutm1 fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, Brd4::Nutm1 can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.

First Report of a SARS-CoV-2 Genome Sequence with a Spike His69-Val70 Deletion and an Asn439Lys Mutation in Morocco.

We report the nearly complete genome sequence and the genetic variations of a clinical sample of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) collected from a nasopharyngeal swab specimen from a male patient from Harhoura-Rabat, Morocco. The sequence, which was obtained using Ion Torrent technology, is valuable as it carries a recently described deletion (His69-Val70) and substitution (Asn439Lys).

Bioinformatics Analysis of Differentially Expressed Genes and miRNAs in Low-Grade Gliomas.

Low-grade glioma is the most common type of primary intracranial tumor. In the last 3 years, new observations of molecular precursors in adults with gliomas have led to a modification in the histopathologic classification of these brain tumors. Among the biomarkers that have been highlighted, we have the micro RNAs (miRNAs) which play a crucial role in the regulation of gene expression and the long noncoding RNAs (lncRNAs) controlling various cellular and metabolic pathways. In our study, large-scale data on sequenced RNA and miRNAs from 516 patients were obtained from the Cancer Genome Atlas database by the TCGAbiolinks package. We identified the differential expression of miRNAs and genes using the Limma package and then we used the ClusterProfiler package for annotations of the biological pathways of the expressed genes, the survival package to estimate the survival analysis, and the GDCRNATools package to determine miRNAs-genes and miRNAs-lncRNAs interactions. We obtained a significant correlation between the miRNAs identified and the overall survival of the patients (log-rank P < .05) and we have theoretically proposed a novel network of miRNAs involved in low-grade gliomas, specifically astrocytomas and oligodendrogliomas, which combine both genes and lncRNAs.

AKT1 Polymorphism (rs10138227) and Risk of Colorectal Cancer in Moroccan Population: A Case Control Study.

BACKGROUND: LMTK3 and AKT1 each have a role in carcinogenesis and tumor progression. The analysis of single nucleotide polymorphisms of AKT1 and LMTK3 could lead to more complete and accurate risk estimates for colorectal cancer. AIM: We evaluated the association between single nucleotide polymorphisms (SNPs) of AKT1 and LMTK3 and the risk of colorectal cancer in a case-control study in Moroccan population. METHODS: Genomic DNA from 70 colorectal cancer patients and 50 healthy control subjects was extracted from whole blood. Genotyping was performed by direct sequencing after polymerase chain reactions for the 7 SNPs (AKT1rs1130214G/T, AKT1rs10138227C/T, AKT1rs3730358C/T, AKT1rs1000559097G/A, AKT1rs2494737A/T, LMTK3rs8108419G/A, and LMTK3rs9989661A/G.). Study subjects provided detailed information during the collection. All P values come from bilateral tests. RESULTS: In the logistic regression analysis, a significantly high risk of colorectal cancer was associated with TC/TT genotypes of rs10138227 with adjusted odds ratio [OR] equal to 2.82 and 95% confidence interval [CI] of 1.15 to 6.91. CONCLUSION: Our results suggest that the SNP AKT1rs10138227 could affect susceptibility to CRC, probably by modulating the transcriptional activity of AKT1. However, larger independent studies are needed to validate our results.

Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas.

INTRODUCTION: The emergence of new omics approaches, such as genomic algorithms to identify tumor mutations and molecular modeling tools to predict the three-dimensional structure of proteins, has facilitated the understanding of the dynamic mechanisms involved in the pathogenesis of low-grade gliomas including oligodendrogliomas and astrocytomas. METHODS: In this study, we targeted known mutations involved in low-grade gliomas, starting with the sequencing of genomic regions encompassing exon 4 of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) and the four exons (5-6 and 7-8) of TP53 from 32 samples, followed by computational analysis to study the impact of these mutations on the structure and function of 3 proteins IDH1, IDH2, and p53. RESULTS: We obtain a mutation that has an effect on the catalytic site of the protein IDH1 as R132H and on the catalytic site of the protein IDH2 as R172M. Other mutations at p53 have been identified as K305N, which is a pathogenic mutation; R175 H, which is a benign mutation; and R158G, which disrupts the structural conformation of the tumor suppressor protein. CONCLUSION: In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests.