Genomic, Epigenomic and Transcriptomic Molecular Characterization of Splenic Marginal Zone Lymphoma Reveals Recurrent Abnormalities in miR-182

Splenic marginal zone lymphoma (SMZL) is a low grade B-cell non-Hodgkin's lymphoma. The molecular pathology of this entity remains poorly understood. To characterise this lymphoma at the molecular level, we performed an integrated analysis of 1) genome wide genetic copy number alterations 2) gene expression profiles and 3) epigenetic DNA methylation profiles.We have previously shown that SMZL is characterised by recurrent alterations of chromosomes 7q, 6q, 3q, 9q and 18; however, gene resolution oligonucleotide array comparative genomic hybridisation did not reveal evidence of cryptic amplification or deletion in these regions. The most frequently lost 7q32 region contains a cluster of miRNAs. qRT-PCR revealed that three of these (miR-182/96/183) show underexpression in SMZL, and miR-182 is somatically mutated in >20% of cases of SMZL, as well as in >20% of cases of follicular lymphoma, and between 5-15% of cases of chronic lymphocytic leukaemia, MALT-lymphoma and hairy cell leukaemia. We conclude that miR-182 is a strong candidate novel tumour suppressor miRNA in lymphoma.The overall gene expression signature of SMZL was found to be strongly distinct fromthose of other lymphomas. Functional analysis of gene expression data revealed SMZL to be characterised by abnormalities in B-cell receptor signalling (especially through the CD19/21-PI3K/AKT pathway) and apoptotic pathways. In addition, genes involved in the response to viral infection appeared upregulated. SMZL shows a unique epigenetic profile, but analysis of differentially methylated genes showed few with methylation related transcriptional deregulation, suggesting that DNA methylation abnormalities are not a critical component of the SMZL malignant phenotype.

BCR and TLR signalling pathways are recurrently targeted by genetic changes in splenic marginal zone lymphomas.

The genetics and pathogenesis of splenic marginal zone lymphoma are poorly understood. The lymphoma lacks chromosome translocation, and ~30% of cases are featured by 7q deletion, but the gene targeted by the deletion is unknown. A recent study showed inactivation of A20, a 'global' NF-kB negative regulator, in 1 of 12 splenic marginal zone lymphoma. To investigate further whether deregulation of the NF-kB pathway plays a role in the pathogenesis of splenic marginal zone lymphoma, we screened several NF-kB regulators for genetic changes by PCR and sequencing. Somatic mutations were found in A20 (6/46=13%), MYD88 (6/46=13%), CARD11 (3/34=8.8%), but not in CD79A, CD79B and ABIN1. Interestingly, these genetic changes are largely mutually exclusive from each other and MYD88 mutation was also mutually exclusive from 7q deletion. These results strongly suggest that deregulation of the TLR (toll like receptor) and BCR (B-cell receptor) signalling pathway may play an important role in the pathogenesis of splenic marginal zone lymphoma.

Characterizing emission and breathing-zone concentrations following exposure cases to fluororesin-based waterproofing spray mists.

Measurements and simulations were performed to assess workers' exposure to solvent vapors and aerosols during the waterproofing of a tiled surface. This investigation followed two recent incidents in the same company where workers experienced acute respiratory illness after spraying a stain-repellent resin containing fluorinated polymers on stone-tiled walls and floors. Because the waterproofing activity had been done for years at the tile company without encountering any exposure problems prior to these cases, it was strongly suspected that the incidents were linked to a recent change in the composition of the coating mixture. Experimental measurements and simulations indicated that the emission rate of particles smaller than 10 microm may be estimated at 0.66 mg/sec (SD 0.10) for the old resin and at 0.37 mg/sec (SD 0.04) for the new one. The measurement of the solvent emission rate from surfaces coated with the two resins indicated that shortly after spraying, the emission was in the range of 18 to 20 mg/sec x m2 and was similar for both products. Solvent and overspray emission rates were introduced in a two-zone compartment model. The results obtained in the near-field indicate significant exposure to overspray mist (7 and 34 mg/m3 for new resin) and solvent vapors (80 to 350 ppm for the new resin). It was also shown that the introduction of the new resin tended to significantly decrease the levels of solvents and particulates in the workers' breathing zone. These results strongly suggest that cases of acute respiratory illness are related to the specific toxicity of the fluorinated polymer itself. The fact that the same polymer is used in various commercial products raises concern regarding other possible occupational and domestic exposures.

Bulletin des armées de la République : réservé à la zone des armées

Périodicité : Quotidien (15 août-9 septembre 1914) ; bi-hebdomadaire (12 septembre 1914-18 mars 1916) ; hebdomadaire (22 mars 1916-décembre 1917)

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1943/07/25 (N21).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1942/07 (N9).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1944/08/25 (N37).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1942/05 (REPRODUCTION).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1942/03 (N1).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1943/08/15 (N22).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1944/04/01 (N30).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1942/02.

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1943/06/01 (N18).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1943/02/20 (N15).

Le Franc-tireur : mensuel dans la mesure du possible et par la grâce de la police du Maréchal ["puis" organe des Mouvements unis de résistance. Edition Zone-Sud]

1944/05/06 (N31).