Menée à l'aide d'un modèle murin transgénique, cette étude met en évidence le rôle de la dismutase SOD1 dans la tumorigenèse mammaire induite par un oncogène

SOD1 is essential for oncogene-driven mammary tumor formation but dispensable for normal development and proliferation

Gomez, Maria L. ; Shah, Nagma ; Kenny, Timothy C. ; Jenkins, Edmund C. ; Germain, Doris

We previously reported that the dismutase SOD1 is overexpressed in breast cancer. However, whether SOD1 plays an active role in tumor formation in vivo has never been demonstrated. Further, as luminal cells of normal breast epithelial cells are enriched in SOD1, whether SOD1 is essential for normal mammary gland development has never been determined. We initiated this study to investigate the role of SOD1 in mammary gland tumorigenesis as well as in normal mammary gland development. We crossed [...]

Cet article analyse le rôle de la plasticité phénotypique dans le développement d'un mélanome, sa progression et sa résistance aux traitements

Phenotype plasticity as enabler of melanoma progression and therapy resistance

Arozarena, Imanol ; Wellbrock, Claudia

Malignant melanoma is notorious for its inter- and intratumour heterogeneity, based on transcriptionally distinct melanoma cell phenotypes. It is thought that these distinct phenotypes are plastic in nature and that their transcriptional reprogramming enables heterogeneous tumours both to undergo different stages of melanoma progression and to adjust to drug exposure during treatment. Recent advances in genomic technologies and the rapidly expanding availability of large gene expression [...]

Menée à partir de l'analyse de l'exome de 118 échantillons biopsiques prélevés sur 23 patients atteints d'un cancer colorectal avec métastases hépatiques ou cérébrales, puis menée sur une cohorte de 2 751 patients supplémentaires, cette étude met en évidence de manière quantitative la dissémination précoce de cellules cancéreuses

Quantitative evidence for early metastatic seeding in colorectal cancer

Hu, Zheng ; Ding, Jie ; Ma, Zhicheng ; Sun, Ruping ; Seoane, Jose A. ; Scott Shaffer, J. ; Suarez, Carlos J. ; Berghoff, Anna S. ; Cremolini, Chiara ; Falcone, Alfredo ; Loupakis, Fotios ; Birner, Peter ; Preusser, Matthias ; Lenz, Heinz-Josef ; Curtis, Christina

Both the timing and molecular determinants of metastasis are unknown, hindering treatment and prevention efforts. Here we characterize the evolutionary dynamics of this lethal process by analyzing exome-sequencing data from 118 biopsies from 23 patients with colorectal cancer with metastases to the liver or brain. The data show that the genomic divergence between the primary tumor and metastasis is low and that canonical driver genes were acquired early. Analysis within a spatial tumor growth [...]

Menée à l'aide de cellules mononucléées du sang périphérique humain, d'échantillons tumoraux et de modèles murins, cette étude met en évidence le rôle du facteur nucléaire TOX dans la régulation de la différenciation des lymphocytes T spécifiques de tumeur

TOX is a critical regulator of tumour-specific T cell differentiation

Scott, Andrew C. ; Dündar, Friederike ; Zumbo, Paul ; Chandran, Smita S. ; Klebanoff, Christopher A. ; Shakiba, Mojdeh ; Trivedi, Prerak ; Menocal, Laura ; Appleby, Heather ; Camara, Steven J. ; Zamarin, Dmitriy ; Walther, Tyler ; Snyder, Alexandra C. ; Femia, Matthew R. ; Comen, Elizabeth A. ; Wen, Hannah Y. ; Hellmann, Matthew D. ; Anandasabapathy, Niroshana ; Liu, Yong ; Altorki, Nasser K. ; Lauer, Peter ; Levy, Olivier ; Glickman, Michael ; Kaye, Jonathan ; Betel, Doron ; Philip, Mary ; Schietinger, Andrea

Tumor-specific CD8 T cell dysfunction is a differentiation state distinct from the functional effector or memory T cell states1–6. Here we identify the nuclear factor, Thymocyte selection-associated HMG box protein, TOX, as a critical regulator of tumor-specific T cell (TST) differentiation. We show that TOX is highly expressed in dysfunctional TST from tumors and in exhausted T cells in chronic viral infection. TOX expression is driven by chronic TCR stimulation and NFAT activation. Ectopic [...]

Menée à l'aide de lignées cellulaires de lymphome diffus à grandes cellules B de type ABC, de xénogreffes sur des modèles murins et à partir de l'analyse génomique de 1 000 échantillons tumoraux, cette étude met en évidence un mécanisme par lequel l'augmentation du nombre de copies de la région chromosomique 18q21.2 dans certaines cellules cancéreuses favorise la surexpression du facteur de transcription TCF4 (E2-2) et l'expression d'immunoglobulines IgM

Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma

Jain, Neeraj ; Hartert, Keenan ; Tadros, Saber ; Fiskus, Warren ; Havranek, Ondrej ; Ma, Man Chun John ; Bouska, Alyssa ; Heavican, Tayla ; Kumar, Dhiraj ; Deng, Qing ; Moore, Dalia ; Pak, Christine ; Liu, Chih Long ; Gentles, Andrew J. ; Hartmann, Elena ; Kridel, Robert ; Smedby, Karin Ekstrom ; Juliusson, Gunnar ; Rosenquist, Richard ; Gascoyne, Randy D. ; Rosenwald, Andreas ; Giancotti, Filippo ; Neelapu, Sattva S. ; Westin, Jason ; Vose, Julie M. ; Lunning, Matthew A. ; Greiner, Timothy ; Rodig, Scott ; Iqbal, Javeed ; Alizadeh, Ash A. ; Davis, R. Eric ; Bhalla, Kapil ; Green, Michael R.

Activated B cell (ABC-like) diffuse large B cell lymphoma (DLBCL) can be curable, but therapies are needed for those who relapse or are refractory to current treatments. Jain et al. found that a percentage of ABC-like DLBCL patient tumors had copy gains on part of chromosome 18. The gains increased expression of transcription factor TCF4 (E2-2), which, in turn, activated immunoglobulin μ and MYC. Finding that tumors with this gain were dependent on TCF4 and that TCF4 was regulated by [...]

Cet article passe en revue les principes fondamentaux des techniques de séquençage de nouvelle génération puis analyse l'apport de ces nouvelles techniques dans la connaissance des cancers du pancréas

Next-Generation Sequencing in Pancreatic Cancer

Shen, Gong-Qing ; Aleassa, Essa M. ; Walsh, R. Matthew ; Morris-Stiff, Gareth

Pancreatic ductal adenocarcinoma (PDAC) is lethal, and the majority of patients present with locally advanced or metastatic disease that is not amenable to cure. Thus, with surgical resection being the only curative modality, it is critical that disease is identified at an earlier stage to allow the appropriate therapy to be applied. Unfortunately, a specific biomarker for early diagnosis has not yet been identified; hence, no screening process exists. Recently, high-throughput screening and [...]