A partir d'échantillons tumoraux prélevés sur 110 patients atteints d'un cancer du poumon à petites cellules, cette étude identifie un ensemble d'anomalies génomiques, notamment des réarrangements du gène TP73 et des mutations inactivant les gènes de la famille NOTCH

Comprehensive genomic profiles of small cell lung cancer

A. list of authors ; affiliations appears at the end of the, paper

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes d'adénocarcinome canalaire du pancréas, cette étude met en évidence des mécanismes par lesquels, en reprogrammant le métabolisme des cellules cancéreuses, les facteurs de transcription de la famille MiT/TFE favorisent la croissance tumorale

Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism

Perera, Rushika M. ; Stoykova, Svetlana ; Nicolay, Brandon N. ; Ross, Kenneth N. ; Fitamant, Julien ; Boukhali, Myriam ; Lengrand, Justine ; Deshpande, Vikram ; Selig, Martin K. ; Ferrone, Cristina R. ; Settleman, Jeff ; Stephanopoulos, Gregory ; Dyson, Nicholas J. ; Zoncu, Roberto ; Ramaswamy, Sridhar ; Haas, Wilhelm ; Bardeesy, Nabeel

Activation of cellular stress response pathways to maintain metabolic homeostasis is emerging as a critical growth and survival mechanism in many cancers. The pathogenesis of pancreatic ductal adenocarcinoma (PDA) requires high levels of autophagy, a conserved self-degradative process. However, the regulatory circuits that activate autophagy and reprogram PDA cell metabolism are unknown. Here we show that autophagy induction in PDA occurs as part of a broader transcriptional program that [...]

Cet article passe en revue les défis posés par la gestion et l'analyse des grandes bases de données produites par les nouvelles technologies en génomique

Big Data: Astronomical or Genomical?

Stephens, Zachary D. ; Lee, Skylar Y. ; Faghri, Faraz ; Campbell, Roy H. ; Zhai, Chengxiang ; Efron, Miles J. ; Iyer, Ravishankar ; Schatz, Michael C. ; Sinha, Saurabh ; Robinson, Gene E.

Genomics is a Big Data science and is going to get much bigger, very soon, but it is not known whether the needs of genomics will exceed other Big Data domains. Projecting to the year 2025, we compared genomics with three other major generators of Big Data: astronomy, YouTube, and Twitter. Our estimates show that genomics is a “four-headed beast”—it is either on par with or the most demanding of the domains analyzed here in terms of data acquisition, storage, distribution, and analysis. We [...]

Cet article passe en revue les perspectives offertes par les outils mathématiques à base de fractales pour modéliser le développement d'un cancer du poumon

Lung cancer - a fractal viewpoint

Lennon, Frances E. ; Cianci, Gianguido C. ; Cipriani, Nicole A. ; Hensing, Thomas A. ; Zhang, Hannah J. ; Chen, Chin-Tu ; Murgu, Septimiu D. ; Vokes, Everett E. ; Vannier, Michael W. ; Salgia, Ravi

Fractals are mathematical constructs that show self-similarity over a range of scales and non-integer (fractal) dimensions. Owing to these properties, fractal geometry can be used to efficiently estimate the geometrical complexity, and the irregularity of shapes and patterns observed in lung tumour growth (over space or time), whereas the use of traditional Euclidean geometry in such calculations is more challenging. The application of fractal analysis in biomedical imaging and time series has [...]