Project description:Characterize the genes deregulated in CD34 positive cells from peripheral blood of FPD/AML patients harbouring two different RUNX1 mutations. RUNX1 (also called AML1), a DNA-binding subunit of the CBF transcription factor family, is a master regulatory gene in hematopoiesis and acts as a tumour suppressor. Heterozygous germ line alterations in RUNX1 lead to a familial platelet disorder with a propensity to develop acute myeloid leukemia (FPD/AML). Although RUNX1 abnormalities per se are not sufficient to induce full-blown leukemia in FPD, this pathology represents a valuable model to understand how RUNX1 germ line mutations predispose to acquisition of additional genetic changes leading to leukemia transformation. To investigate how RUNX1 may predispose to leukemia, we performed a comparative study between two pedigrees harbouring different RUNX1 mutations, one associated with only thrombocytopenia (R139stop) and the other leading to thrombocytopenia and leukemic predisposition (R174Q).
Project description:Detection of causal variant for thrombocytopenia and second hit causing malignant disease onset by next-generation sequencing. The sample was taken at MDS diagnosis, the illness later developed into AML.
Project description:In a subset of imprinting disorders caused by epimutations, multiple imprinted loci are affected. We have investigated the clinical and molecular features of a familial DNA methylation disorder.
Project description:In a subset of imprinting disorders caused by epimutations, multiple imprinted loci are affected. We have investigated the clinical and molecular features of a familial DNA methylation disorder. Bisulphite converted DNA from the 60 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip