A partir de données génomiques et transcriptomiques issues d'échantillons tumoraux prélevés au diagnostic et à la récidive sur 114 patients atteints d'un glioblastome, cette étude met en évidence l'évolution clonale induite par les traitements

Clonal evolution of glioblastoma under therapy

Wang, Jiguang ; Cazzato, Emanuela ; Ladewig, Erik ; Frattini, Veronique ; Rosenbloom, Daniel I. S. ; Zairis, Sakellarios ; Abate, Francesco ; Liu, Zhaoqi ; Elliott, Oliver ; Shin, Yong-Jae ; Lee, Jin-Ku ; Lee, In-Hee ; Park, Woong-Yang ; Eoli, Marica ; Blumberg, Andrew J. ; Lasorella, Anna ; Nam, Do-Hyun ; Finocchiaro, Gaetano ; Iavarone, Antonio ; Rabadan, Raul

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. To better understand how GBM evolves, we analyzed longitudinal genomic and transcriptomic data from 114 patients. The analysis shows a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern, together with estimates of evolutionary rate, suggests that relapse-associated clones typically existed years before diagnosis. Fifteen percent of tumors [...]

Cet article passe en revue les travaux récents sur la génomique des tumeurs germinales testiculaires

The genomic landscape of testicular germ cell tumours: from susceptibility to treatment

Litchfield, Kevin ; Levy, Max ; Huddart, Robert A. ; Shipley, Janet ; Turnbull, Clare

The genomic landscape of testicular germ cell tumour (TGCT) can be summarized using four overarching hypotheses. Firstly, TGCT risk is dominated by inherited genetic factors, which determine nearly half of all disease risk and are highly polygenic in nature. Secondly KIT-KITLG signalling is currently the major pathway that is implicated in TGCT formation, both as a predisposition risk factor and a somatic driver event. Results from genome-wide association studies have also consistently [...]

Cet article passe en revue les travaux récents sur le rôle de mutations affectant les gènes de facteurs d'épissage de l'ARN dans les processus de cancérogenèse

RNA splicing factors as oncoproteins and tumour suppressors

Dvinge, Heidi ; Kim, Eunhee ; Abdel-Wahab, Omar ; Bradley, Robert K.

The recent genomic characterization of cancers has revealed recurrent somatic point mutations and copy number changes affecting genes encoding RNA splicing factors. Initial studies of these 'spliceosomal mutations' suggest that the proteins bearing these mutations exhibit altered splice site and/or exon recognition preferences relative to their wild-type counterparts, resulting in cancer-specific mis-splicing. Such changes in the splicing machinery may create novel vulnerabilities in cancer [...]

Cet article passe en revue les travaux récents sur le rôle des neutrophiles dans le développement et la progression d'une tumeur

Neutrophils in cancer: neutral no more

Coffelt, Seth B. ; Wellenstein, Max D. ; de Visser, Karin E.

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour [...]

Menée in vitro, in vivo et à partir d'échantillons tumoraux prélevés sur 123 patients atteints d'un cancer du poumon non à petites cellules, cette étude met en évidence des mécanismes par lesquels la protéine MSI2 favorise le processus métastatique

Musashi-2 (MSI2) supports TGF-β signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis

Kudinov, Alexander E. ; Deneka, Alexander ; Nikonova, Anna S. ; Beck, Tim N. ; Ahn, Young-Ho ; Liu, Xin ; Martinez, Cathleen F. ; Schultz, Fred A. ; Reynolds, Samuel ; Yang, Dong-Hua ; Cai, Kathy Q. ; Yaghmour, Khaled M. ; Baker, Karmel A. ; Egleston, Brian L. ; Nicolas, Emmanuelle ; Chikwem, Adaeze ; Andrianov, Gregory ; Singh, Shelly ; Borghaei, Hossein ; Serebriiskii, Ilya G. ; Gibbons, Don L. ; Kurie, Jonathan M. ; Golemis, Erica A. ; Boumber, Yanis

Non-small cell lung cancer (NSCLC) has a 5-y survival rate of ∼16%, with most deaths associated with uncontrolled metastasis. We screened for stem cell identity-related genes preferentially expressed in a panel of cell lines with high versus low metastatic potential, derived from NSCLC tumors of KrasLA1/+;P53R172H