A partir d'échantillons tumoraux prélevés sur 193 patients atteints d'un carcinome hépatocellulaire, cette étude française met en évidence l’insertion d’une partie d’ARN viral associé à l’adénovirus de type 2 dans le génome des cellules tumorales de 11 patients

Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas

Nault, Jean-Charles ; Datta, Shalini ; Imbeaud, Sandrine ; Franconi, Andrea ; Mallet, Maxime ; Couchy, Gabrielle ; Letouzé, Eric ; Pilati, Camilla ; Verret, Benjamin ; Blanc, Jean-Frederic ; Balabaud, Charles ; Calderaro, Julien ; Laurent, Alexis ; Letexier, Melanie ; Bioulac-Sage, Paulette ; Calvo, Fabien ; Zucman-Rossi, Jessica

Hepatocellular carcinomas (HCCs) are liver tumors related to various etiologies, including alcohol intake and infection with hepatitis B (HBV) or C (HCV) virus. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We found clonal integration of adeno-associated virus type 2 (AAV2) in 11 of 193 HCCs. These AAV2 integrations occurred in known cancer driver genes, namely CCNA2 (cyclin A2; four cases), TERT (telomerase reverse transcriptase; [...]

A partir de lignées cellulaires et d'échantillons tumoraux prélevés sur des patients atteints d'un lymphome T cutané (mycose fungoïde ou syndrome de Sézary), cette étude met en évidence la présence de mutations du gène codant le récepteur TNFR2 dans les tumeurs de 18% des patients

Genomic analysis of mycosis fungoides and Sezary syndrome identifies recurrent alterations in TNFR2

Ungewickell, Alexander ; Bhaduri, Aparna ; Rios, Eon ; Reuter, Jason ; Lee, Carolyn S. ; Mah, Angela ; Zehnder, Ashley ; Ohgami, Robert ; Kulkarni, Shashikant ; Armstrong, Randall ; Weng, Wen-Kai ; Gratzinger, Dita ; Tavallaee, Mahkam ; Rook, Alain ; Snyder, Michael ; Kim, Youn ; Khavari, Paul A.

Mycosis fungoides and Sézary syndrome comprise the majority of cutaneous T cell lymphomas (CTCLs), disorders notable for their clinical heterogeneity that can present in skin or peripheral blood. Effective treatment options for CTCL are limited, and the genetic basis of these T cell lymphomas remains incompletely characterized1. Here we report recurrent point mutations and genomic gains of TNFRSF1B, encoding the tumor necrosis factor receptor TNFR2, in 18% of patients with mycosis fungoides and [...]

Cet article passe en revue les travaux récents menés à l'aide de modèles précliniques pour étudier les mécanismes par lesquels, de façon paradoxale, des traitements anticancéreux sont susceptibles de favoriser le processus métastatique

Prodding the Beast: Assessing the Impact of Treatment-Induced Metastasis

Ebos, John M.L.

The arsenal of treatments for most cancers fit broadly into the categories of surgery, chemotherapy, radiation, and targeted therapy. All represent proven and successful strategies, yet each can trigger local (tumor) and systemic (host) processes that elicit unwanted, often opposing, influences on cancer growth. Under certain conditions, nearly all cancer treatments can facilitate metastatic spread, often in parallel (and sometimes in clear contrast) with tumor reducing benefits. The paradox of [...]

Cet article compare les capacités de la théorie des mutations somatiques et de la théorie du champ d'organisation tissulaire à rendre compte du processus métastatique

Cancer Metastases: So Close and So Far

Sonnenschein, Carlos ; Soto, Ana M.

Metastases are tumors that develop at a distance from their primary origin and are responsible for the death of 90% of cancer patients. For over a century the notion of seed (migrating cells) and soil (the locus where those cells anchor) provided an accurate account of which were the protagonists in their genesis. Despite aggressive efforts to unravel the dynamics involving migrating cells and the niche in which they anchor, explanations of this process remain ill-defined and controversial. The [...]

Cet article passe en revue les travaux récents sur le rôle des glycanes dans le développement et la progression d'un cancer

Glycosylation in cancer: mechanisms and clinical implications

Pinho, Salome S. ; Reis, Celso A.

Despite recent progress in understanding the cancer genome, there is still a relative delay in understanding the full aspects of the glycome and glycoproteome of cancer. Glycobiology has been instrumental in relevant discoveries in various biological and medical fields, and has contributed to the deciphering of several human diseases. Glycans are involved in fundamental molecular and cell biology processes occurring in cancer, such as cell signalling and communication, tumour cell dissociation [...]

Cet article passe en revue les travaux récents sur les modèles animaux mis en oeuvre pour étudier le processus métastatique

Studying cancer metastasis: existing models, challenges and future perspectives

Marion, Denise M. S. van ; Domanska, Urszula M. ; Timmer-Bosscha, Hetty ; Walenkamp, Annemiek M. E.

Cancer metastasis causes most cancer-related deaths. Several model systems to study the complex and multi step process of metastasis exist, including in vitro systems, ex-vivo organ slices, Drosophila Melanogaster and zebrafish models and the use of the chorio allantoic membrane (CAM) of fertilized chicken eggs. These models are relatively easy and cheap but often lack the opportunity to study the complete metastasis cascade. More complex but also more expensive is the use of animal models [...]

Menée à l'aide de modèles murins, cette étude montre que des populations hétérogènes de cellules cancéreuses sont susceptibles d'acquérir une compétence métastatique sans l'apparition de nouvelles mutations

Metastatic competence can emerge with selection of pre-existing oncogenic alleles without a need of new mutations

Jacob, Leni S. ; Vanharanta, Sakari ; Obenauf, Anna C. ; Pirun, Mono ; Viale, Agnes ; Socci, Nicholas D ; Massagué, Joan

Several experimental models faithfully recapitulate many important facets of human metastatic disease. Here we have performed whole exome sequencing in five widely used experimental metastasis models that were independently derived through in vivo selection from heterogeneous human cancer cell lines. In addition to providing an important characterization of these model systems, our study examines the genetic evolution of metastatic phenotypes. We found that in vivo selected highly metastatic [...]

Menée à l'aide d'un modèle murin de cancer du pancréas, cette étude met en évidence la dynamique cellulaire de l'évolution tumorale et le rôle joué par l'hétérogénéité clonale dans le processus métastatique

Pancreatic Cancer Metastases Harbor Evidence of Polyclonality

Maddipati, Ravikanth ; Stanger, Ben Z.

Studies of the cancer genome have demonstrated that tumors are comprised of multiple sub-clones with varied genetic and phenotypic properties. However, little is known about how metastases arise and evolve from these sub-clones. To understand the cellular dynamics that drive metastasis, we used multi-color lineage tracing technology in an autochthonous mouse model of pancreatic cancer. Here, we report that precursor lesions exhibit significant clonal heterogeneity but that this diversity [...]

Menée à l'aide de modèles murins de cancer du sein triplement négatif, cette étude met en évidence des mécanismes par lesquels, en régulant les macrophages associés aux tumeurs, la protéine RKIP réprime le processus invasif

Metastasis suppressors regulate the tumor microenvironment by blocking recruitment of pro-metastatic tumor-associated macrophages

Frankenberger, Casey ; Rabe, Daniel ; Bainer, Russell ; Sankarasharma, Devipriya ; Chada, Kiran ; Krausz, Thomas ; Gilad, Yoav ; Becker, Lev ; Rosner, Marsha Rich

Triple-negative breast cancer (TNBC) patients have the highest risk of recurrence and metastasis. Because they cannot be treated with targeted therapies, and many do not respond to chemotherapy, they represent a clinically underserved group. TNBC is characterized by reduced expression of metastasis suppressors such as Raf Kinase Inhibitory Protein (RKIP), which inhibits tumor invasiveness. Mechanisms by which metastasis suppressors alter tumor cells are well characterized; however, their [...]

Cet article passe en revue les travaux récents sur le rôle joué par les réseaux de transduction de signal, internes aux cellules cancéreuses, dans les mécanismes de prolifération cellulaire, le processus invasif et la résistance thérapeutique

The dynamic control of signal transduction networks in cancer cells

Kolch, Walter ; Halasz, Melinda ; Granovskaya, Marina ; Kholodenko, Boris N.

Cancer is often considered a genetic disease. However, much of the enormous plasticity of cancer cells to evolve different phenotypes, to adapt to challenging microenvironments and to withstand therapeutic assaults is encoded by the structure and spatiotemporal dynamics of signal transduction networks. In this Review, we discuss recent concepts concerning how the rich signalling dynamics afforded by these networks are regulated and how they impinge on cancer cell proliferation, survival, [...]