Menée à l'aide d'une technique de séquençage à haut débit sur 4 864 échantillons tumoraux prélevés sur des patients atteints d'un cancer, cette étude analyse la fréquence d'anomalies affectant des gènes impliqués dans la voie de signalisation du cycle cellulaire

Cell cycle gene alterations in 4864 tumors analyzed by next generation sequencing:  Implications for targeted therapeutics

Helsten, Teresa ; Kato, Shumei ; Schwaederle, Maria ; Tomson, Brett N. ; Buys, Timon P.H. ; Elkin, Sheryl K. ; Carter, Jennifer L. ; Kurzrock, Razelle

Alterations in the cyclin-dependent kinase (CDK)-retinoblastoma (Rb) machinery disrupt cell cycle regulation and are being targeted in drug development. In order to understand the cancer types impacted by this pathway, we analyzed frequency of abnormalities in key cell cycle genes across 4864 tumors using next-generation sequencing (182 or 236 genes) (Clinical Laboratory Improvement Amendments [CLIA] laboratory). Aberrations in the cell cycle pathway were identified in 39% of cancers, making [...]

A partir de données issues du projet "The Cancer Genome Atlas" (13 types de cancer), cette étude met en évidence des profils moléculaires différents selon le sexe des patients

Comprehensive Characterization of Molecular Differences in Cancer between Male and Female Patients

Yuan, Yuan ; Liu, Lingxiang ; Chen, Hu ; Wang, Yumeng ; Xu, Yanxun ; Mao, Huzhang ; Li, Jun ; Mills, Gordon B ; Shu, Yongqian ; Li, Liang ; Liang, Han

An individual's sex has been long recognized as a key factor affecting cancer incidence, prognosis, and treatment responses. However, the molecular basis for sex disparities in cancer remains poorly understood. We performed a comprehensive analysis of molecular differences between male and female patients in 13 cancer types of The Cancer Genome Atlas and revealed two sex-effect groups associated with distinct incidence and mortality profiles. One group contains a small number of sex-affected [...]

A partir d'échantillons de liquide péritonéal prélevés sur 17 patientes atteintes d'un carcinome séreux ovarien de haut grade et sur 20 témoins, cette étude évalue l'efficacité d'une technique de séquençage ultra-profond pour identifier des mutations du gène TP53

Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues

Krimmel, Jeffrey D. ; Schmitt, Michael W. ; Harrell, Maria I. ; Agnew, Kathy J. ; Kennedy, Scott R. ; Emond, Mary J. ; Loeb, Lawrence A. ; Swisher, Elizabeth M. ; Risques, Rosa Ana

Current sequencing methods are error-prone, which precludes the identification of low frequency mutations for early cancer detection. Duplex sequencing is a sequencing technology that decreases errors by scoring mutations present only in both strands of DNA. Our aim was to determine whether duplex sequencing could detect extremely rare cancer cells present in peritoneal fluid from women with high-grade serous ovarian carcinomas (HGSOCs). These aggressive cancers are typically diagnosed at a [...]

A partir d'échantillons tumoraux prélevés sur 680 patients atteints d'un adénocarcinome du poumon et 484 patients atteints d'un carcinome épidermoïde du poumon, cette étude identifie des anomalies génomiques spécifiques pour chacun des deux types de cancer du poumon

Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas

Campbell, Joshua D. ; Alexandrov, Anton ; Kim, Jaegil ; Wala, Jeremiah ; Berger, Alice H. ; Pedamallu, Chandra Sekhar ; Shukla, Sachet A. ; Guo, Guangwu ; Brooks, Angela N. ; Murray, Bradley A. ; Imielinski, Marcin ; Hu, Xin ; Ling, Shiyun ; Akbani, Rehan ; Rosenberg, Mara ; Cibulskis, Carrie ; Ramachandran, Aruna ; Collisson, Eric A. ; Kwiatkowski, David J. ; Lawrence, Michael S. ; Weinstein, John N. ; Verhaak, Roel G. W. ; Wu, Catherine J. ; Hammerman, Peter S. ; Cherniack, Andrew D. ; Getz, Gad ; Cancer Genome Atlas Research, Network ; Artyomov, Maxim N. ; Schreiber, Robert ; Govindan, Ramaswamy ; Meyerson, Matthew

To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in [...]

Menée in vitro et in vivo sur des modèles de cancer de l'estomac, cette étude met en évidence des mécanismes par lesquels le long ARN non codant GClnc1 favorise la prolifération des cellules cancéreuses ainsi que les processus invasif et métastatique

A novel lncRNA GClnc1 promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern

Sun, Tian-Tian ; He, Jie ; Liang, Qian ; Ren, Lin-Lin ; Yan, Ting-Ting ; Yu, Ta-Chung ; Tang, Jia-Yin ; Bao, Yu-Jie ; Hu, Ye ; Lin, Yanwei ; Sun, Danfeng ; Chen, Ying-Xuan ; Hong, Jie ; Chen, Haoyan ; Zou, Weiping ; Fang, Jing-Yuan

Long non-coding RNAs (lncRNAs) play a role in carcinogenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown. In this study, we identified a novel lncRNA, GClnc1, which was upregulated and associated with tumorigenesis, tumor size, metastasis, and poor prognosis in gastric cancer. GClnc1 affected gastric cancer cell proliferation, invasiveness, and metastasis in multiple gastric cancer models. Mechanistically, GClnc1 bound WDR5 (a key component of histone [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en activant la signalisation Wnt, l'enzyme USP6 exerce une fonction d'oncogène

USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds

Madan, Babita ; Walker, Matthew P. ; Young, Robert ; Quick, Laura ; Orgel, Kelly A. ; Ryan, Meagan ; Gupta, Priti ; Henrich, Ian C. ; Ferrer, Marc ; Marine, Shane ; Roberts, Brian S. ; Arthur, William T. ; Berndt, Jason D. ; Oliveira, Andre M. ; Moon, Randall T. ; Virshup, David M. ; Chou, Margaret M. ; Major, Michael B.

The Wnt signaling pathways play pivotal roles in carcinogenesis. Modulation of the cell-surface abundance of Wnt receptors is emerging as an important mechanism for regulating sensitivity to Wnt ligands. Endocytosis and degradation of the Wnt receptors Frizzled (Fzd) and lipoprotein-related protein 6 (LRP6) are regulated by the E3 ubiquitin ligases zinc and ring finger 3 (ZNRF3) and ring finger protein 43 (RNF43), which are disrupted in cancer. In a genome-wide small interfering RNA screen, we [...]

Menée sur le rat-taupe nu, un rongeur naturellement résistant au cancer, cette étude met en évidence un puissant mécanisme suppresseur de tumeurs dans les cellules souches pluripotentes induites

Tumour resistance in induced pluripotent stem cells derived from naked mole-rats

Miyawaki, Shingo ; Kawamura, Yoshimi ; Oiwa, Yuki ; Shimizu, Atsushi ; Hachiya, Tsuyoshi ; Bono, Hidemasa ; Koya, Ikuko ; Okada, Yohei ; Kimura, Tokuhiro ; Tsuchiya, Yoshihiro ; Suzuki, Sadafumi ; Onishi, Nobuyuki ; Kuzumaki, Naoko ; Matsuzaki, Yumi ; Narita, Minoru ; Ikeda, Eiji ; Okanoya, Kazuo ; Seino, Ken-ichiro ; Saya, Hideyuki ; Okano, Hideyuki ; Miura, Kyoko

The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, lorsqu'elle est sécrétée par les cellules de mélanome et les macrophages associés aux tumeurs, une flavoprotéine favorise la croissance tumorale

Renalase expression by melanoma and tumor associated-macrophages promotes tumor growth through a STAT3-mediated mechanism

Hollander, Lindsay ; Guo, Xiaojia ; Velazquez, Heino ; Chang, John ; Safirstein, Robert ; Kluger, Harriet M ; Cha, Charles ; Desir, Gary

To sustain their proliferation cancer cells overcome negative-acting signals that restrain their growth and promote senescence and cell death. Renalase (RNLS) is a secreted flavoprotein that functions as a survival factor after ischemic and toxic injury, signaling through the plasma calcium channel PMCA4b to activate the PI3K/AKT and MAPK pathways. We show that RNLS expression is increased markedly in primary melanomas and CD163+ tumor associated macrophages (TAM). In clinical specimens, RNLS [...]

Menée à l'aide de modèles murins de cancer de la prostate, cette étude met en évidence des mécanismes par lesquels, en activant la signalisation ERK5, le facteur de transcription FOXF1 favorise la croissance tumorale

The transcription factor FOXF1 promotes prostate cancer by stimulating the mitogen-activated protein kinase ERK5

Fulford, Logan ; Milewski, David ; Ustiyan, Vladimir ; Ravishankar, Navin ; Cai, Yuqi ; Le, Tien ; Masineni, Sreeharsha ; Kasper, Susan ; Aronow, Bruce ; Kalinichenko, Vladimir V. ; Kalin, Tanya V.

Some types of prostate cancer can be aggressive, and these metastatic forms of the disease have few treatment options. Fulford et al. found that prostate tumors from some patients express the gene encoding the transcription factor forkhead box F1 (FOXF1), which is not expressed in normal prostate epithelium. Overexpressing FOXF1 increased tumor growth and metastatic progression when tumor cells were implanted into mice. FOXF1 bound to and increased the expression of genes encoding the kinase [...]

Cet article passe en revue les travaux récents sur la biologie des carcinomes épidermoïdes

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

Dotto, G.  Paolo ; Rustgi, Anil K

Squamous cell carcinomas (SCCs) represent the most frequent human solid tumors and are a major cause of cancer mortality. These highly heterogeneous tumors arise from closely interconnected epithelial cell populations with intrinsic self-renewal potential inversely related to the stratified differentiation program. SCCs can also originate from simple or pseudo-stratified epithelia through activation of quiescent cells and/or a switch in cell-fate determination. Here, we focus on specific [...]