Refractory anaemia with ring sideroblasts (RARS) is distinguished by hyperplastic inefficient erythropoiesis, aberrant mitochondrial ferritin accumulation and anaemia. Heterozygous mutations in the spliceosome gene SF3B1 are found in a majority of RARS cases. To explore the link between SF3B1 mutations and anaemia, we studied mutated RARS CD34(+) marrow cells with regard to transcriptome sequen...

BACKGROUND Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and...

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration and loss of motor neurons in the spinal cord, brainstem and motor cortex. Up to 10% of ALS cases are inherited (familial, fALS) and associated with mutations, frequently in the superoxide dismutase 1 (SOD1) gene. Rodent transgenic models of ALS are often used to elucidate a complex patho...

During aging phenotypic changes in the hematopoietic system occur, and possible reason of these can be accumulation gene mutations stem cells or early blood progenitors. Although are mostly neutral, some may give progenitor a proliferative advantage. In this case clonal hematopoiesis will arise, which is characterized by formation genetically distinct subpopulation cells. Clonal become basis fo...

The majority of tumors from hereditary nonpolyposis colorectal cancer families and a subset of unselected gastrointestinal and endometrial tumors exhibit a microsatellite mutator phenotype (MMP) that leads to the accumulation of hundreds of thousands of clonal mutations in simple repeat sequences. The mutated genes with positive or negative roles in cell growth or survival in aneuploid gastroin...

As the first draft of the human genome nears completion, we are faced with the challenge of defining the functions of the 70,000–100,000 genes contained within the sequence. A powerful combination of large-scale forward genetics and elegant cellular analysis ensures that the zebrafish will have an important role in the functional analysis of the vertebrate genome. Genetic screens have identifie...

BACKGROUND & AIMS Hepatocellular carcinoma develops in patients with chronic hepatitis or cirrhosis via a stepwise accumulation of various genetic alterations. To explore the genetic basis of development of hepatocellular carcinoma in hepatitis C virus (HCV)-associated chronic liver disease, we evaluated genetic variants that accumulate in nontumor cirrhotic liver. METHODS We determined the w...

Lymphoma is the most common hematological malignancy in developed countries. Outcome is strongly determined by molecular subtype, reflecting a need for new and improved treatment options. Dogs spontaneously develop lymphoma, and the predisposition of certain breeds indicates genetic risk factors. Using the dog breed structure, we selected three lymphoma predisposed breeds developing primarily T...

The majority of tumors from hereditary nonpolyposis colorectal cancer families and a subset of unselected gastrointestinal and endometrial tumors exhibit a microsatellite mutator phenotype (MMP) that leads to the accumulation of hundreds of thousands of clonal mutations in simple repeat sequences. The mutated genes with positive or negative roles in cell growth or survival in aneuploid gastroin...

Primary myelofibrosis (PMF), a BCR-ABL negative myeloproliferative neoplasm, is heterogeneous clinical and genetic disorder with poor prognosis. We aimed to study the mutational profile of driver genes (JAK2, CALR, MPL) high-molecular-risk (HMR) (ASXL1, EZH2, IDH1/2, SRSF2) their prognostic impact in 65 Argentine patients PMF. Mutually exclusive mutations were identified 88% cases HMR detected ...