Enhanced overexpression of an HIF-1/hypoxia-related protein in cancer cells.

Cap43 is a protein whose RNA is induced under conditions of severe hypoxia or prolonged elevations of intracellular calcium. Additionally, Ni and Co also induce Cap43 because they produce a state of hypoxia in cells. Cap43 protein is expressed at low levels in normal tissues; however, in a variety of cancers, including lung, brain, melanoma, liver, prostate, breast, and renal cancers, Cap43 protein is overexpressed in cancer cells. The low level of expression of Cap43 in some normal tissues compared with their cancerous counterparts, combined with the high stability of Cap43 protein and mRNA, makes the Cap43 gene a new, important cancer marker. We hypothesize that the mechanism of Cap43 overexpression in cancer cells involves a state of hypoxia characteristic of cancer cells where the Cap43 protein becomes a signature for this hypoxic state

Mecanismes de regulation de la lymphopoiese B impliquesdans deux lymphopathies malignes de type B : le myelome multiple et la leucemie lymphoide chronique

CNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

DE-kupl: exhaustive capture of biological variation in RNA-seq data through k-mer decomposition

DE-kupl is a computational protocol that aims to capture all k-mer variation in an input set of RNA-seq libraries. This protocol is composed of four main components : Indexing: index and count all k-mers (k=31) in the input libraries Filtering: delete k-mers representing potential sequencing errors or perfectly matching known transcripts Differential Expression (DE): select k-mers with significantly different abundance across conditions Assembly and annotation: build contigs of assembled k-mers and annotate contigs based on sequence alignment

Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells

Experimentele farmacotherapi

New chimeric RNAs in acute myeloid leukemia [version 2; referees: 2 approved]

Background: High-throughput next generation sequencing (NGS) technologies enable the detection of biomarkers used for tumor classification, disease monitoring and cancer therapy. Whole-transcriptome analysis using RNA-seq is important, not only as a means of understanding the mechanisms responsible for complex diseases but also to efficiently identify novel genes/exons, splice isoforms, RNA editing, allele-specific mutations, differential gene expression and fusion-transcripts or chimeric RNA (chRNA). Methods: We used Crac, a tool that uses genomic locations and local coverage to classify biological events and directly infer splice and chimeric junctions within a single read. Crac’s algorithm extracts transcriptional chimeric events irrespective of annotation with a high sensitivity, and CracTools was used to aggregate, annotate and filter the chRNA reads. The selected chRNA candidates were validated by real time PCR and sequencing.  In order to check the tumor specific expression of chRNA, we analyzed a publicly available dataset using a new tag search approach. Results:  We present data related to acute myeloid leukemia (AML) RNA-seq analysis. We highlight novel biological cases of chRNA, in addition to previously well characterized leukemia chRNA. We have identified and validated 17 chRNAs among 3 AML patients: 10 from an AML patient with a translocation between chromosomes 15 and 17 (AML-t(15;17), 4  from patient with normal karyotype (AML-NK) 3 from a patient with chromosomal 16 inversion (AML-inv16). The new fusion transcripts can be classified into four groups according to the exon organization. Conclusions:  All groups suggest complex but distinct synthesis mechanisms involving either collinear exons of different genes, non-collinear exons, or exons of different chromosomes. Finally, we check tumor-specific expression in a larger RNA-seq AML cohort and identify new AML biomarkers that could improve diagnosis and prognosis of AML