Menée sur différents types de cancer, cette étude identifie un "module d'hyperméthylation de l'ADN" comprenant un ensemble de gènes associés à une signature de cellule souche du cancer

A DNA hypermethylation module for the stem/progenitor cell signature of cancer

Easwaran, Hariharan ; Johnstone, Sarah ; VanNeste, Leander ; Ohm, Joyce ; Mosbruger, Tim ; Wang, Qiuju ; Aryee, Martin J ; Joyce, Patrick ; Ahuja, Nita ; Weisenberger, Dan ; Collisson, Eric ; Zhu, Jing-chun ; Yegnasubramanian, Srinivasan ; Matsui, William ; Baylin, Stephen B

Many DNA-hypermethylated cancer genes are occupied by the polycomb (PcG) repressor complex in embryonic stem cells (ESC). Their prevalence in the full spectrum of cancers, the exact context of chromatin involved, and their status in adult cell renewal systems are unknown. Using a genome-wide analysis, we demonstrate that approximately 75% of hypermethylated genes are marked by PcG in the context of bivalent chromatin in both ESC and adult stem/progenitor cells. A large number of these genes are [...]

Menée sur un patient atteint d'une leucémie lymphoblastique aiguë présentant la fusion BCR-ABL1, cette étude de séquençage global du transcriptome analyse les différences d'expression des gènes entre des prélèvements effectués lors du diagnostic et au moment d'une récidive

Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia

Iacobucci, I. ; Ferrarini, A. ; Sazzini, M. ; Giacomelli, E. ; Lonetti, A. ; Xumerle, L. ; Ferrari, A. ; Papayannidis, C. ; Malerba, G. ; Luiselli, D. ; Boattini, A. ; Garagnani, P. ; Vitale, A. ; Soverini, S. ; Pane, F. ; Baccarani, M. ; Delledonne, M. ; Martinelli, G.

Although the pathogenesis of BCR–ABL1-positive acute lymphoblastic leukemia (ALL) is mainly related to the expression of the BCR–ABL1 fusion transcript, additional cooperating genetic lesions are supposed to be involved in its development and progression. Therefore, in an attempt to investigate the complex landscape of mutations, changes in expression profiles and alternative splicing (AS) events that can be observed in such disease, the leukemia transcriptome of a BCR–ABL1-positive ALL patient [...]

Menée sur des souris génétiquement modifiées pour que leurs cellules expriment un niveau élevé de la protéine PTEN, cette étude met en évidence un mécanisme de régulation négative du métabolisme des cellules tumorales par PTEN

Systemic Elevation of PTEN Induces a Tumor-Suppressive Metabolic State

Garcia-Cao, Isabel ; Song, Min Sup ; Hobbs, Robin M ; Laurent, Gaelle ; Giorgi, Carlotta ; de Boer, Vincent C J. ; Anastasiou, Dimitrios ; Ito, Keisuke ; Sasaki, Atsuo T ; Rameh, Lucia ; Carracedo, Arkaitz ; Vander Heiden, Matthew G ; Cantley, Lewis C ; Pinton, Paolo ; Haigis, Marcia C ; Pandolfi, Pier Paolo

Decremental loss of PTEN results in cancer susceptibility and tumor progression. PTEN elevation might therefore be an attractive option for cancer prevention and therapy. We have generated several transgenic mouse lines with PTEN expression elevated to varying levels by taking advantage of bacterial artificial chromosome (BAC)-mediated transgenesis. The Super-PTEN mutants are viable and show reduced body size due to decreased cell number, with no effect on cell size. Unexpectedly, PTEN [...]

Menée à l'aide de modèles murins, cette étude met en évidence un mécanisme immunitaire par lequel l'enzyme CD73 favorise la tumorigenèse

CD73-deficient mice are resistant to carcinogenesis

Stagg, John ; Beavis, Paul A ; Divisekera, Upulie ; Liu, Mira CP ; Moeller, Andreas ; Darcy, Phillip K ; Smyth, Mark J

CD73 is a cell surface 5'-nucleotidase that converts AMP to adenosine, an immune suppressive molecule. CD73 may promote immune escape in cancer by contributing to the degradation of extracellular ATP released by dying cancer cells in hypoxic tumors or following chemotherapy. However, whether CD73 exerts a critical oncogenic function during tumorigenesis is unknown. In this study, we used genetically deficient mice to investigate its contribution to autochthonous tumor formation. CD73 deficiency [...]

Menée à l'aide de modèles murins, cette étude met en évidence un mécanisme épigénétique par lequel le complexe PRC2 régule le développement et la progression d'une leucémie myéloïde aiguë

Polycomb repressive complex 2 is required for MLL-AF9 leukemia

Neff, Tobias ; Sinha, Amit U. ; Kluk, Michael J. ; Zhu, Nan ; Khattab, Mohamed H. ; Stein, Lauren ; Xie, Huafeng ; Orkin, Stuart H. ; Armstrong, Scott A.

A growing body of data suggests the importance of epigenetic mechanisms in cancer. Polycomb repressive complex 2 (PRC2) has been implicated in self-renewal and cancer progression, and its components are overexpressed in many cancers. However, its role in cancer development and progression remains unclear. We used conditional alleles for the PRC2 components enhancer of zeste 2 (Ezh2) and embryonic ectoderm development (Eed) to characterize the role of PRC2 function in leukemia development and [...]

Menée in vitro et in vivo, cette étude met en évidence un mécanisme par lequel le gène P14ARF joue un rôle de suppresseur de tumeurs en inhibant l'angiogenèse induite par un gliome

P14ARF inhibits human glioblastoma–induced angiogenesis by upregulating the expression of TIMP3

Zerrouqi, Abdessamad ; Pyrzynska, Beata ; Febbraio, Maria ; Brat, Daniel J. ; Van Meir, Erwin G.

Malignant gliomas are the most common and the most lethal primary brain tumors in adults. Among malignant gliomas, 60%–80% show loss of P14ARF tumor suppressor activity due to somatic alterations of the INK4A/ARF genetic locus. The tumor suppressor activity of P14ARF is in part a result of its ability to prevent the degradation of P53 by binding to and sequestering HDM2. However, the subsequent finding of P14ARF loss in conjunction with TP53 gene loss in some tumors suggests the protein may [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence le rôle joué par le micro-ARN29b dans la régulation de la voie de signalisation de la transition épithélio-mésenchymateuse et le processus métastatique

MicroRNA-29b Suppresses Prostate Cancer Metastasis by Regulating Epithelial-Mesenchymal Transition Signaling

Ru, Peng ; Steele, Robert ; Newhall, Philip ; Phillips, Nancy J. ; Toth, Karoly ; Ray, Ratna B.

Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients; however, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment are necessary for inhibiting prostate cancer disease progression. Here, we have shown that microRNA-29b (miR-29b) expression was lower in prostate cancer cells (PC3 and LNCaP) as compared to immortalized prostate [...]

Menée in vitro, cette étude met en évidence un mécanisme par lequel la protéine Twist favorise la motilité des cellules souches du cancer et le processus métastatique

RAC1 activation mediates Twist1-induced cancer cell migration

Yang, Wen-Hao ; Lan, Hsin-Yi ; Huang, Chi-Hung ; Tai, Shyh-Kuan ; Tzeng, Cheng-Hwai ; Kao, Shou-Yen ; Wu, Kou-Juey ; Hung, Mien-Chie ; Yang, Muh-Hwa

Epithelial–mesenchymal transition (EMT), which is characterized by the suppression of the adhesion protein E-cadherin, is a crucial process that promotes metastasis and stem-like properties of cancer cells. However, the dissociation of cellular aggregates is not sufficient to explain why cancer cells move, and the motile nature of cancer cells undergoing EMT remains elusive. Here, we identify a mechanism in which the EMT inducer Twist1 elicits cancer cell movement through activation of RAC1. [...]

Cet article passe en revue les avantages et les limites des technologies à haut débit mises en oeuvre pour déterminer le profil d'expression des gènes dans un contexte de traitement personnalisé des cancers

Gene expression profiling to dissect the complexity of cancer biology: pitfalls and promise

Raspe, Eric ; Decraene, Charles ; Berx, Geert

Despite advances in chemotherapy, hormone therapy and radiotherapy, not all cancer patients respond favorably to treatment. However, progress in understanding the mechanisms of malignant diseases and the mode of action of therapies are opening opportunities to match treatment to specific patient subpopulations, paving the way for personalised medicine. In this context, high throughput technologies that have been developed to determine gene expression profiles potentially offer an effective tool [...]