Menée sur des données issues du projet "The Cancer Genome Atlas" (échantillons tumoraux prélevés sur des patients atteints d'un glioblastome ou d'un gliome de bas grade), cette étude utilise une méthode de visualisation numérique pour identifier notamment 8 sous-types de gliome à partir d'informations moléculaires

Big data visualization identifies the multidimensional molecular landscape of human gliomas

Bolouri, Hamid ; Zhao, Lue Ping ; Holland, Eric C.

We show that visualizing large molecular and clinical datasets enables discovery of molecularly defined categories of highly similar patients. We generated a series of linked 2D sample similarity plots using genome-wide single nucleotide alterations (SNAs), copy number alterations (CNAs), DNA methylation, and RNA expression data. Applying this approach to the combined glioblastoma (GBM) and lower grade glioma (LGG) The Cancer Genome Atlas datasets, we find that combined CNA/SNA data divide [...]

A partir de 3 bases de données indépendantes portant sur des échantillons tumoraux prélevés sur des patients atteints d'une tumeur urothéliale, cette étude identifie une association entre des mutations somatiques du gène ERCC2, un gène du système de réparation par excision de nucléotides, et une signature mutationnelle dont l'activité est reliée au tabagisme

Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors

Kim, Jaegil ; Mouw, Kent W. ; Polak, Paz ; Braunstein, Lior Z. ; Kamburov, Atanas ; Tiao, Grace ; Kwiatkowski, David J. ; Rosenberg, Jonathan E. ; Van Allen, Eliezer M. ; D'Andrea, Alan D. ; Getz, Gad

Alterations in DNA repair pathways are common in tumors and can result in characteristic mutational signatures; however, a specific mutational signature associated with somatic alterations in the nucleotide- excision repair (NER) pathway has not yet been identified. Here we examine the mutational processes operating in urothelial cancer, a tumor type in which the core NER gene ERCC2 is significantly mutated. Analysis of three independent urothelial tumor cohorts demonstrates a strong [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence des mécanismes de nature métabolique par lesquels la perte constitutionnelle d'expression du gène PKM2 favorise le développement d'un carcinome hépatocellulaire

Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma

Dayton, Talya L. ; Gocheva, Vasilena ; Miller, Kathryn M. ; Israelsen, William J. ; Bhutkar, Arjun ; Clish, Clary B. ; Davidson, Shawn M. ; Luengo, Alba ; Bronson, Roderick T. ; Jacks, Tyler ; Vander Heiden, Matthew G.

Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2-null mice (Pkm2−/−). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2−/− mice are viable and fertile. Thus, PKM2 is not [...]

Menée in vivo, cette étude met en évidence des mécanismes par lesquels, dans le micro-environnement fibrillaire d'une tumeur mammaire, des anomalies génomiques favorisent le glissement de cellules cancéreuses sur d'autres cellules et, ce faisant, le processus métastatique

Regulators of Metastasis Modulate the Migratory Response to Cell Contact under Spatial Confinement

Milano, Daniel F ; Ngai, Nicholas A ; Muthuswamy, Senthil K ; Asthagiri, Anand R

The breast tumor microenvironment (TMEN) is a unique niche where protein fibers help to promote invasion and metastasis. Cells migrating along these fibers are constantly interacting with each other. How cells respond to these interactions has important implications. Cancer cells that circumnavigate or slide around other cells on protein fibers take a less tortuous path out of the primary tumor; conversely, cells that turn back upon encountering other cells invade less efficiently. The contact [...]

Cet article passe en revue les travaux récents sur l'évolution d'un mélanome métastatique à partir de mélanocytes

From melanocytes to melanomas

Shain, A. Hunter ; Bastian, Boris C.

Melanomas on sun-exposed skin are heterogeneous tumours, which can be subtyped on the basis of their cumulative levels of exposure to ultraviolet (UV) radiation. A melanocytic neoplasm can also be staged by how far it has progressed, ranging from a benign neoplasm, such as a naevus, to a malignant neoplasm, such as a metastatic melanoma. Each subtype of melanoma can evolve through distinct evolutionary trajectories, passing through (or sometimes skipping over) various stages of transformation. [...]