Project description:The NOTCH1-driven MYC enhancer (NMe) is essential for T cell development, transformation and the development of acute lymphoblastic leukemia. Here we analyze by RNAseq the gene expression profile of DN3 thymocytes from NMe wild type and NMe GATA site 1 and 2 (GS1+2) homozygous mutant mice. GSEA analysis show a significant enrichment of MYC signature genes, consistent with a deficient function of NMe in GATA site 1 and 2 homozygous mutant thymocytes.
Project description:The NOTCH1-driven MYC enhancer (NMe) is essential for T cell development, transformation and the development of acute lymphoblastic leukemia. Here we analyze chromatin accessibility by ATACseq in DN3 thymocytes and Notch-induced TALL blasts from NMe wild type and NMe GATA site 1 and 2 (GS1+2) homozygous mutant mice.
Project description:The NOTCH1-driven MYC enhancer (NMe) is essential for T cell development, transformation and the development of acute lymphoblastic leukemia. Here we analyzed by single-cell RNAseq the gene expression profile of total thymus from NMe wild type and NMe GATA site 1 and 2 (GS1+2) homozygous mutant mice.
Project description:We investigated the cause of gastrointestinal neoplasia in a man who developed adenocarcinoma of the ampulla of Vater at the age of 34, followed almost three decades later by adenomatous polyps and invasive adenocarcinomas of both the colon and stomach. Premature chromatid separation, mosaic variegated aneuploidy (MVA), combined with structural chromosome abnormalities were detected in his cells. We identified a homozygous intronic mutation, c.2386-11A>G in BUB1B which creates a de novo splice site that is favored over the authentic site. This study expands the phenotype of BUB1B mutations and MVA to include common adult-onset cancers and provides evidence for the interdependency of APC and BUBR1 proteins in humans.