Cet article passe en revue les travaux récents sur l'identification d'anomalies génomiques dans les cancers du sein

From Integrative Genomics to Therapeutic Targets

Natrajan, Rachael ; Wilkerson, Paul

Combinatorial approaches that integrate conventional pathology with genomic profiling and functional genomics have begun to enhance our understanding of the genetic basis of breast cancer. These methods have identified key genotypic–phenotypic correlations in different breast cancer subtypes that have led to the discovery of genetic dependencies that drive their behavior. Moreover, this knowledge has been applied to define novel tailored therapies for these groups of patients with cancer. With [...]

Menée sur 38 patientes présentant un léiomyome utérin, cette étude identifie de fréquents réarrangements chromosomiques complexes évocateurs d'un phénomène de chromothripsis

Characterization of Uterine Leiomyomas by Whole-Genome Sequencing

Mehine, Miika ; Kaasinen, Eevi ; Mäkinen, Netta ; Katainen, Riku ; Kämpjärvi, Kati ; Pitkänen, Esa ; Heinonen, Hanna-Riikka ; Butzow, Ralf ; Kilpivaara, Outi ; Kuosmanen, Anna ; Ristolainen, Heikki ; Gentile, Massimiliano ; Sjöberg, Jari ; Vahteristo, Pia ; Aaltonen, Lauri A.

Background : Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. Methods : We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. Results : Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex [...]

Menée in vitro, cette étude met en évidence le rôle joué par la signalisation STAT3 dans le développement d'une leucémie aiguë lymphopblastique présentant la translocation t(12;21)

STAT3 mediates oncogenic addiction to TEL-AML1 in t(12;21) acute lymphoblastic leukemia

Mangolini, Maurizio ; de Boer, Jasper ; Walf-Vorderwülbecke, Vanessa ; Pieters, Rob ; den Boer, Monique L. ; Williams, Owen

The t(12;21)(p13;q22) translocation is the most common chromosomal abnormality in pediatric leukemia. Although this rearrangement involves two well characterized transcription factors, TEL and AML1, the molecular pathways affected by the result of the translocation remain largely unknown. Also in light of recent studies showing genetic and functional heterogeneities in cells responsible for cancer clone maintenance and propagation, targeting a single common deregulated pathway may be critical [...]

Menée in vitro et in vivo, cette étude met en évidence un réseau de gènes régulés par le proto-oncogène MLL et impliqués dans l'hématopoïèse normale ou les leucémies

An MLL-dependent network sustains hematopoiesis

Artinger, Erika L. ; Mishra, Bibhu P. ; Zaffuto, Kristin M. ; Li, Bin E. ; Chung, Elaine K. Y. ; Moore, Adrian W. ; Chen, Yufei ; Cheng, Chao ; Ernst, Patricia

The histone methyltransferase Mixed Lineage Leukemia (MLL) is essential to maintain hematopoietic stem cells and is a leukemia protooncogene. Although clustered homeobox genes are well-characterized targets of MLL and MLL fusion oncoproteins, the range of Mll-regulated genes in normal hematopoietic cells remains unknown. Here, we identify and characterize part of the Mll-dependent transcriptional network in hematopoietic stem cells with an integrated approach by using conditional [...]

Menée in vitro et in vivo, cette étude met en évidence le rôle joué par l'enzyme Prx2 dans la régulation des processus invasif et métastatique d'un mélanome

Peroxiredoxin-2 represses melanoma metastasis by increasing E-cadherin/β-catenin complexes in adherens junctions

Lee, Doo Jae ; Kang, Dong Hoon ; Choi, Mina ; Choi, Yang Ji ; Lee, Joo Young ; Park, Joo Hyun ; Park, Yoon Jung ; Lee, Kyung Wha ; Kang, Sang Won

In melanoma, transition to the vertical growth phase is the critical step in conversion to a deadly malignant disease. Here we offer the first evidence that an antioxidant enzyme has a key role in this transition. We found that the antioxidant enzyme peroxiredoxin-2 (Prx2) inversely correlated with the metastatic capacity of human melanoma cells. Silencing Prx2 expression stimulated proliferation and migration, whereas ectopic expression of Prx2 produced the opposite effect. Mechanistic [...]

Cet article présente le consortium américain "Electronic Medical Records and Genomics Network" qui développe des méthodes et des recommandations pour l'usage de dossiers médicaux électroniques à des fins de recherche en génomique

The Electronic Medical Records and Genomics (eMERGE) Network: past, present, and future

Gottesman, Omri ; Kuivaniemi, Helena ; Tromp, Gerard ; Faucett, W. Andrew ; Li, Rongling ; Manolio, Teri A. ; Sanderson, Saskia C. ; Kannry, Joseph ; Zinberg, Randi ; Basford, Melissa A. ; Brilliant, Murray ; Carey, David J. ; Chisholm, Rex L. ; Chute, Christopher G. ; Connolly, John J. ; Crosslin, David ; Denny, Joshua C. ; Gallego, Carlos J. ; Haines, Jonathan L. ; Hakonarson, Hakon ; Harley, John ; Jarvik, Gail P. ; Kohane, Isaac ; Kullo, Iftikhar J. ; Larson, Eric B. ; McCarty, Catherine ; Ritchie, Marylyn D. ; Roden, Dan M. ; Smith, Maureen E. ; Bottinger, Erwin P. ; Williams, Marc S.

The Electronic Medical Records and Genomics Network is a National Human Genome Research Institute–funded consortium engaged in the development of methods and best practices for using the electronic medical record as a tool for genomic research. Now in its sixth year and second funding cycle, and comprising nine research groups and a coordinating center, the network has played a major role in validating the concept that clinical data derived from electronic medical records can be used [...]