Menée à l'aide d'une technique de séquençage massivement parallèle sur des échantillons tumoraux prélevés sur 99 patients afro-américains atteints d'un cancer du poumon non à petites cellules, cette étude analyse les anomalies génomiques somatiques présentes dans les tumeurs et les compare avec les anomalies détectées chez des patients d'origine européenne

Genomic Characterization of Non–Small-Cell Lung Cancer in African Americans by Targeted Massively Parallel Sequencing

Araujo, Luiz H. ; Timmers, Cynthia ; Bell, Erica Hlavin ; Shilo, Konstantin ; Lammers, Philip E. ; Zhao, Weiqiang ; Natarajan, Thanemozhi G. ; Miller, Clinton J. ; Zhang, Jianying ; Yilmaz, Ayse S. ; Liu, Tom ; Coombes, Kevin ; Amann, Joseph ; Carbone, David P.

Purpose : Technologic advances have enabled the comprehensive analysis of genetic perturbations in non–small-cell lung cancer (NSCLC); however, African Americans have often been underrepresented in these studies. This ethnic group has higher lung cancer incidence and mortality rates, and some studies have suggested a lower incidence of epidermal growth factor receptor mutations. Herein, we report the most in-depth molecular profile of NSCLC in African Americans to date. Methods : A custom panel [...]

Cet article passe en revue les travaux récents sur la neurofibromatose de type 1, une maladie génétique conférant une susceptibilité aux cancers

A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor

Ratner, Nancy ; Miller, Shyra J.

Neurofibromatosis type 1 (NF1) is a common genetic disorder that predisposes affected individuals to tumours. The NF1 gene encodes a RAS GTPase-activating protein called neurofibromin and is one of several genes that (when mutant) affect RAS-MAPK signalling, causing related diseases collectively known as RASopathies. Several RASopathies, beyond NF1, are cancer predisposition syndromes. Somatic NF1 mutations also occur in 5-10% of human sporadic cancers and may contribute to resistance to [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence des mécanismes par lesquels, dans les cellules hématopoïétiques, la perte d'expression du gène TET2 favorise le développement d'une leucémie

Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis

Rasmussen, Kasper D. ; Jia, Guangshuai ; Johansen, Jens V. ; Pedersen, Marianne T. ; Rapin, Nicolas ; Bagger, Frederik O. ; Porse, Bo T. ; Bernard, Olivier A. ; Christensen, Jesper ; Helin, Kristian

DNA methylation is tightly regulated throughout mammalian development, and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CG dinucleotide (CpG) islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles [...]

Menée à l'aide d'une xénogreffe, cette étude met en évidence des mécanismes par lesquels, en activant les neurones du micro-environnement tumoral, une protéine synaptique (NLGN3) favorise la prolifération des cellules d'un gliome

Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion

Venkatesh, Humsa S ; Johung, Tessa B ; Caretti, Viola ; Noll, Alyssa ; Tang, Yujie ; Nagaraja, Surya ; Gibson, Erin M ; Mount, Christopher W ; Polepalli, Jai ; Mitra, Siddhartha S ; Woo, Pamelyn J ; Malenka, Robert C ; Vogel, Hannes ; Bredel, Markus ; Mallick, Parag ; Monje, Michelle

Active neurons exert a mitogenic effect on normal neural precursor and oligodendroglial precursor cells, the putative cellular origins of high-grade glioma (HGG). By using optogenetic control of cortical neuronal activity in a patient-derived pediatric glioblastoma xenograft model, we demonstrate that active neurons similarly promote HGG proliferation and growth in vivo. Conditioned medium from optogenetically stimulated cortical slices promoted proliferation of pediatric and adult [...]

Menée sur 20 lignées cellulaires et quatre échantillons tumoraux prélevés sur des patientes atteintes d'un cancer du sein triplement négatif, cette étude dresse un catalogue des niveaux d'expression de quelque 12 000 protéines différentes

The Proteomic Landscape of Triple-Negative Breast Cancer

Lawrence, Robert T ; Perez, Elizabeth M ; Hernández, Daniel ; Miller, Chris P ; Haas, Kelsey M ; Irie, Hanna Y ; Lee, Su-In ; Blau, C.  Anthony ; Villén, Judit

Triple-negative breast cancer is a heterogeneous disease characterized by poor clinical outcomes and a shortage of targeted treatment options. To discover molecular features of triple-negative breast cancer, we performed quantitative proteomics analysis of twenty human-derived breast cell lines and four primary breast tumors to a depth of more than 12,000 distinct proteins. We used this data to identify breast cancer subtypes at the protein level and demonstrate the precise quantification of [...]