ABSTRACT: High number of chromosomal copy number aberrations inversely relates to t(11 19)(q21 p13) translocation status in Mucoepidermoid Carcinoma of the Salivary Glands
Project description:genomic analysis using arrayCGH to gain insight into chromosomal copy number in mucoepidermoid carcinoma (MEC). Results suggest that two types of MECs can be distinguished: (i) a group of MECs without t(11;19)(q21;p13) translocation with many copy number aberrations (> 6), independent of histological grade, and (ii) a group of MECs with the t(11;19)(q21;p13) translocation with no or a few copy number aberrations (<6 ) with two exceptions classified as low and intermediate grade.
Project description:We used mRNA expression arrays and integrated analysis to study mucoepidermoid carcinomas (MEC) to identify potential drivers involved with its pathogenesis. Normal salivary glands were used as controls.
Project description:We used miRNA expression arrays and integrated analysis to study mucoepidermoid carcinomas (MEC) to identify potential drivers involved with its pathogenesis. Normal salivary glands were used as controls.
Project description:To further exploration of pathological progress in mucoepidermoid carcinoma, we have employed lncRNA microarray expression profiling and coding transcripts as a discovery platform to identify genes or lncRNAs with the potential to mediate the tumorigenesis of mucopidermoid carcinoma. Normal salivary glands were used as controls.
Project description:Acute myeloid leukemia (AML) in children with cytogenetic aberrations like translocation t(7;12)(q36;p13) is associated with inferior outcome. The translocation can lead to a fusion transcript MNX1::ETV6 but also to activation of MNX1 transcription. We generated an AML mouse model by transplantation of fetal liver cells with ectopic expression of MNX1. AML was highly penetrant in immunocompromised and less penetrant in immunocompetent mice. Transforming capacity was restricted to fetal liver cells and could not achieved with adult bone marrow cells, in concordance with the clinical finding that t(7;12)(q36;p13) is mostly restricted to infants. Ectopic expression of MNX1 led to increased H3K4methylation and reduced H3K27me3, possibly through its interaction with methyl transferases. MNX1 expression was accompanied with changes in genome wide chromatin accessibility , increased DNA damage, depletion in the LSK population and skewing toward the myeloid lineage. These effects, together with leukemia development, could be prevented by the S-adenosylmethionine analogue Sinefungin that acts as a SAM competitor and a pan methyltranferases inhibitor. Expression profiles of a human iPSC AML model with t(7;12) and of TARGET pediatric AML and TCGA patients support the rationale for targeting MNX1 and downstream pathways.
