Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci.

Multiple regulatory elements distant from their targets on the linear genome can influence the expression of a single gene through chromatin looping. Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. However, detection of functional enhancer-promoter interactions is precluded by its effective resolution that is determined by both restriction fragmentation and sensitivity of the experiment.

K313dup is a recurrent CEBPA mutation in de novo acute myeloid leukemia (AML).

The CEBPA gene codes for a transcription factor that has a pivotal role in controlling proliferation and differentiation of myeloid progenitors. Acquired CEBPA mutations have been found in acute myeloid leukemias (AML) with a good prognosis, and most of these patients have a normal karyotype. In this paper, we report four cases that displayed the same K313dup in the CEBPA gene.

Uniparental disomy may be associated with microsatellite instability in acute myeloid leukemia (AML) with a normal karyotype.

The discovery of underlying genetic lesions helps to better understand the mechanisms of leukemogenesis and identify prognostic subgroups. Recent insights have allowed normal karyotype acute myeloid leukemia (AML) to be split into many molecular entities according to the genetic status of FLT3, NPM, CEBPA and MLL. Genome-wide single nucleotide polymorphism analysis was performed on 22 well-characterised AML patients with a normal karyotype.

Epigenetic-based treatments emphasize the biologic differences of core-binding factor acute myeloid leukemias.

Acute myeloid leukemia (AML) is a heterogeneous group of disorders characterized by an abnormal proliferation of the myeloid precursors and a maturation block. The most common chromosomal lesions in AML are the t(8;21) and inv(16). To better understand the leukemogenic mechanism of these fusion proteins, we performed gene expression studies in samples from (8;21), AML1 mutated and inv(16) patients, as well as from the Kasumi-1 cell line and a U937 cell line expressing the AML1-ETO fusion gene.

High expression of CEACAM6 and CEACAM8 mRNA in acute lymphoblastic leukemias.

CEACAM family members are a set of widely expressed proteins involved in several biological functions, including cell adhesion, migration, signal transduction, and the regulation of gene expression. Abnormal overexpression and downregulation of some CEACAMs have been described in tumor cells. Monoclonal antibodies grouped in the CD66 cluster recognize CEACAM members.

A new D816 c-KIT gene mutation in refractory AML1-ETO leukemia.

One of the most common genetic events in acute myeloid leukemia (AML) is the t(8;21) (q22;q22) translocation, which contributes to leukemic transformation. However, different lines of evidence suggest that the AML1-ETO rearrangement is not sufficient to cause the full leukemic phenotype. Secondary genetic alterations such as mutations in receptor tyrosine kinases are thus required to induce overt AML.

Acute myeloid leukemia subgroups identified by pathway-restricted gene expression signatures.

Acute myeloid leukemia (AML) is a heterogeneous group of disorders characterized by abnormal proliferation of myeloid precursors and a maturation block. Underlying genetic lesions determine an altered expression program (transcriptosome) that can be studied in depth by massive technologies. Alternatively, we selected a pathway profiling strategy based on the current knowledge in order to stratify de novo AML patients and identify those cases which would potentially benefit from the use of new chemotherapeutic agents.

Role of gamma-glutamyl cysteine synthetase (gamma-GCS) gene expression as marker of drug sensitivity in acute myeloid leukemias.

Background: Elevated levels of glutathione (GSH) have been reported to play an important role in mediating chemoresistance in tumor cells. The regulation of gamma-glutamylcysteine synthetase (gamma-GCS) is one of the major determinants of GSH homeostasis. The aim of our study was to investigate gamma-GCS gene expression in patients affected by acute myeloid leukemia (AML).

Microsatellite instability is not an uncommon finding in adult de novo acute myeloid leukemia.

To investigate the biologic relevance of microsatellite instability (MSI) in de novo acute myeloid leukemia (AML), 102 consecutive adult patients were analyzed by using a panel of seven microsatellites (BAT25, BAT26, D13S1267, D13S174, D2S123, D5S346 and Mdf15). Frame-shift mutations in the repetitive sequences in the coding region of MSH3, MSH6, BAX, TGFBRII and IGFRII were also investigated by using a fluorescent PCR-based assay. Methylation-specific PCR was used to determine the methylation status of hMLH1 in MSI+ cases.

FLT3 mutations are associated with other molecular lesions in AML.

The basic molecular defects underlying acute myeloid leukemias (AML) seem to be caused by inactivating mutations in transcription factors which control normal myeloid differentiation (Class II mutations) and genetic lesions in tyrosine kinases resulting in constitutive activation (Class I mutations). We sought to determine the frequency of associated mutations (Class I + Class II) in a consecutive series of adult de novo AML (353 patients) in order to stress the validity of this model. Mutations and rearrangements at the FLT3, AML1/ETO, CBFbeta/MYH11, AML1, CEBPalpha and MLL genes were investigated using standard molecular methods.

Id4 is deregulated by a t(6;14)(p22;q32) chromosomal translocation in a B-cell lineage acute lymphoblastic leukemia.

Background And Objectives: Chromosome translocations resulting in gene overexpression are commonly associated with lymphoid neoplasia. Enhancer elements of the immunoglobulin or T-cell receptor (TCR) loci are abnormally located in the vicinity of the entire coding sequences of genes which exert an influence on the normal maturation and differentiation program of lymphoid cells.

Design And Methods: A patient who presented with a B-cell lineage acute lymphoblastic leukemia had a t(6;14)(p22;q32).

Interstitial deletions at the long arm of chromosome 13 may be as common as monosomies in multiple myeloma. A genotypic study.

Background And Objectives: Deletions at the long arm of chromosome 13, mostly at the q14, and monosomy of chromosome 13 are described to be common in multiple myeloma (MM). 13q- has been associated with an adverse outcome and it has been proposed as one of the most important prognostic factors for MM patients. Deletions of 13q14 are rare in monoclonal gammopathy of undetermined significance (MGUS) and are thus believed to be associated with the development of the full myeloma phenotype.