Menée à partir de données pathologiques, génomiques et immunohistochimiques portant sur 30 patients atteints d'un cancer colorectal et ayant survécu à un cancer non séminomateux du testicule, cette étude met en évidence une fréquence élevée de mutations somatiques au niveau des gènes impliqués dans la réparation des mésappariements de l'ADN

Somatic hits in mismatch repair genes in colorectal cancer among non-seminoma testicular cancer survivors

Ykema, Berbel L. M. ; Breekveldt, Emilie C. H. ; Carvalho, Beatriz ; van Wezel, Tom ; Meijer, Gerrit A. ; Kerst, Martijn ; Schaapveld, Michael ; van Leeuwen, Flora E. ; Snaebjornsson, Petur ; van Leerdam, Monique E.

Background : Non-seminoma testicular cancer survivors (TCS) have an increased risk of developing colorectal cancer (CRC) when they have been treated with platinum-based chemotherapy. Previously we demonstrated that among Hodgkin lymphoma survivors (HLS) there is enrichment of rare mismatch repair (MMR) deficient (MMRd) CRCs with somatic hits in MMR genes. We speculate that this phenomenon could also occur among other cancer survivors. We therefore aim to determine the MMR status and its [...]

Menée à l'aide de lignées cellulaires de glioblastome et de modèles murins, cette étude met en évidence un mécanisme par lequel la ligase HECTD3 régule la tumorigenèse via la poly-ubiquitination de la polymérase PARP1 et l'activation de la voie de signalisation du récepteur EGFR

HECTD3 regulates the tumourigenesis of glioblastoma by polyubiquitinating PARP1 and activating EGFR signalling pathway

Zhang, Guanghui ; Tan, Ruoyue ; Wan, Sicheng ; Yang, Rui ; Hu, Xiaosong ; Zhao, Erhu ; Ding, Xiangfei ; Zhang, Jingping ; Li, Biao ; Liang, Ping ; Cui, Hongjuan

Background : The E3 ubiquitin ligase HECTD3 is a homologue of the E6-related protein carboxyl terminus, which plays a crucial role in biological processes and tumourigenesis. However, the functional characterisation of HECTD3 in glioblastoma is still elusive. Methods : Determination of the functional role of HECTD3 in glioblastoma was made by a combination of HECTD3 molecular pattern analysis from human glioblastoma databases and subcutaneous and in situ injections of tumours in mice models. [...]

Cet article passe en revue les découvertes récentes concernant l'effet des anomalies du cycle cellulaire sur le métabolisme des cellules cancéreuses et le processus métastatique

Out of the cycle: Impact of cell cycle aberrations on cancer metabolism and metastasis

Cheung, Alvin Ho-Kwan ; Hui, Chris Ho-Lam ; Wong, Kit Yee ; Liu, Xiaoli ; Chen, Bonan ; Kang, Wei ; To, Ka Fai

The use of cell cycle inhibitors has necessitated a better understanding of the cell cycle in tumour biology to optimize the therapeutic approach. Cell cycle aberrations are common in cancers, and it is increasingly acknowledged that these aberrations exert oncogenic effects beyond the cell cycle. Multiple facets such as cancer metabolism, immunity, and metastasis are also affected, all of which are beyond the effect of cell proliferation alone. This review comprehensively summarized the [...]

Cet article présente une approche, combinant modélisation mathématique et inférence statistique, pour déterminer l'évolution de néoplasies myéloprolifératives et mettre en place des stratégies de dépistage

Inferring the initiation and development of myeloproliferative neoplasms

Hermange, Gurvan ; Rakotonirainy, Alicia ; Bentriou, Mahmoud ; Tisserand, Amandine ; El-Khoury, Mira ; Girodon, François ; Marzac, Christophe ; Vainchenker, William ; Plo, Isabelle ; Cournède, Paul-Henry

The developmental history of blood cancer begins with mutation acquisition and the resulting malignant clone expansion. The two most prevalent driver mutations found in myeloproliferative neoplasms—JAK2V617F and CALRm—occur in hematopoietic stem cells, which are highly complex to observe in vivo. To circumvent this difficulty, we propose a method relying on mathematical modeling and statistical inference to determine disease initiation and dynamics. Our findings suggest that CALRm mutations [...]

A l'aide d'une analyse immunohistochimique par fluorescence d'échantillons tumoraux prélevés sur 636 patients atteints d'un cancer du poumon non à petites cellules, cette étude examine la corrélation entre différents sous-types de fibroblastes associés au cancer et la présence de mutations "conductrices", les caractéristiques immunitaires du microenvironnement tumoral et la survie

Fibroblast subsets in non-small cell lung cancer: associations with survival, mutations, and immune features

Pellinen, Teijo ; Paavolainen, Lassi ; Martín-Bernabé, Alfonso ; Papatella Araujo, Renata ; Strell, Carina ; Mezheyeuski, Artur ; Backman, Max ; La Fleur, Linnea ; Brück, Oscar ; Sjölund, Jonas ; Holmberg, Erik ; Välimäki, Katja ; Brunnström, Hans ; Botling, Johan ; Moreno-Ruiz, Pablo ; Kallioniemi, Olli ; Micke, Patrick ; Ostman, Arne

Cancer-associated fibroblasts (CAFs) are molecularly heterogeneous mesenchymal cells that interact with malignant cells and immune cells and confer both anti- and pro-tumorigenic functions. Prior in situ profiling studies of human CAFs have largely relied on scoring single markers, thus presenting a very limited view of their molecular complexity. Our objective was to study the complex spatial tumor microenvironment of non-small cell lung cancer (NSCLC) with multiple CAF biomarkers, identify [...]