Menée à partir du séquençage de l'ADN d'échantillons de tumeur primitive et de métastases prélevés sur 35 patients atteints d'un mélanome métastatique de l'uvée, cette étude analyse l'apparition d'anomalies génétiques intratumorales au cours du développement de la maladie

The genetic evolution of metastatic uveal melanoma

Shain, A. Hunter ; Bagger, Mette M. ; Yu, Richard ; Chang, Darwin ; Liu, Shanshan ; Vemula, Swapna ; Weier, Jingly F. ; Wadt, Karin ; Heegaard, Steffen ; Bastian, Boris C. ; Kiilgaard, Jens F.

Uveal melanoma is a clinically distinct and particularly lethal subtype of melanoma originating from melanocytes in the eye. Here, we performed multi-region DNA sequencing of primary uveal melanomas and their matched metastases from 35 patients. We observed previously unknown driver mutations and established the order in which these and known driver mutations undergo selection. Metastases had genomic alterations distinct from their primary tumors; metastatic dissemination sometimes occurred [...]

Menée à partir de l'analyse de 122 échantillons bronchiques prélevés sur 77 fumeurs ou anciens fumeurs (âge médian : 62 ans ; 15 femmes), cette étude démontre que le processus d'activation du système immunitaire et le processus d'échappement immunitaire précèdent l'invasion tumorale dans la carcinogenèse épidermoïde précoce

Immune evasion before tumour invasion in early lung squamous carcinogenesis

Mascaux, Celine ; Angelova, Mihaela ; Vasaturo, Angela ; Beane, Jennifer ; Hijazi, Kahkeshan ; Anthoine, Geraldine ; Buttard, Benedicte ; Rothe, Francoise ; Willard-Gallo, Karen ; Haller, Annick ; Ninane, Vincent ; Burny, Arsène ; Sculier, Jean-Paul ; Spira, Avi ; Galon, Jérôme

Early detection and treatment are critical for improving the outcome of patients with cancer1. Understanding the largely uncharted biology of carcinogenesis requires deciphering molecular processes in premalignant lesions, and revealing the determinants of the intralesional immune reaction during cancer development. The adaptive immune response within tumours has previously been shown to be strongest at the earliest stage of carcinoma2,3. Here we show that immune activation and immune escape [...]

Menée à l'aide de lignées cellulaires de cancer mammaire et à l'aide de modèles murins, cette étude démontre que la voie de signalisation NOTCH2 favorise la dormance des cellules cancéreuses et la migration de ces dernières vers le tissu osseux

Notch2 pathway mediates breast cancer cellular dormancy and mobilisation in bone and contributes to haematopoietic stem cell mimicry

Capulli, Mattia ; Hristova, Dayana ; Valbret, Zoé ; Carys, Kashmala ; Arjan, Ronak ; Maurizi, Antonio ; Masedu, Francesco ; Cappariello, Alfredo ; Rucci, Nadia ; Teti, Anna

Background : Recurrence after >5-year disease-free survival affects one-fifth of breast cancer patients and is the clinical manifestation of cancer cell reactivation after persistent dormancy. Methods : We investigated cellular dormancy in vitro and in vivo using breast cancer cell lines and cell and molecular biology techniques. Results : We demonstrated cellular dormancy in breast cancer bone metastasis, associated with haematopoietic stem cell (HSC) mimicry, in vivo competition for HSC [...]

Cet article analyse le rôle des fibroblastes associés au cancer (CAFs) dans le développement tumoral, identifie les mécanismes d'action et passe en revue les stratégies thérapeutiques axées sur les CAFs

Cancer-associated fibroblasts—heroes or villains?

Gieniec, Krystyna A. ; Butler, Lisa M. ; Worthley, Daniel L. ; Woods, Susan L.

Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in vitro and in vivo experiments, pathological association and, more recently, ablation, and it is now widely appreciated that CAFs form a group of highly heterogeneous cells with no single overarching marker. Studies have demonstrated that the [...]

Menée à l'aide d'organoïdes et de xénogreffes sur des modèles murins, cette étude met en évidence le rôle d'un long ARN non codant dans l'activation de la kinase PLK1 et la survie des cellules cancéreuses

The Role of APAL/ST8SIA6-AS1 lncRNA in PLK1 Activation and Mitotic Catastrophe of Tumor Cells

Luo, Man-Li ; Li, Jingjing ; Shen, Liping ; Chu, Junjun ; Guo, Qiannan ; Liang, Guorun ; Wu, Wei ; Chen, Jianing ; Chen, Rufu ; Song, Erwei

Background : Tumor growth can be addicted to vital oncogenes, but whether long non-coding RNAs (lncRNAs) are essential to cancer survival is largely uncharacterized. Methods : We retrieved GEO datasets to identify lncRNAs overexpression in 257 cancers versus 196 normal tissues and analyzed the association of ST8SIA6-AS1 (termed Aurora A/PLK1 associated lncRNA, APAL) with the clinical outcomes of multiple types of cancer from the public RNA-seq and microarray datasets, as well as from in-house [...]