A partir d'échantillons tumoraux prélevés sur 56 patients atteints d'un lymphome à cellules du manteau, cette étude met en évidence diverses mutations somatiques en association avec des anomalies épigénétiques liées à l'état de la chromatine dans les lymphocytes B

The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells

Zhang, Jenny ; Jima, Dereje ; Moffitt, Andrea B. ; Liu, Qingquan ; Czader, Magdalena ; Hsi, Eric D. ; Fedoriw, Yuri ; Dunphy, Cherie H. ; Richards, Kristy L. ; Gill, Javed I. ; Sun, Zhen ; Love, Cassandra ; Scotland, Paula ; Lock, Eric ; Levy, Shawn ; Hsu, David S. ; Dunson, David ; Dave, Sandeep S.

In this study, we define the genetic landscape of mantle cell lymphoma through exome sequencing of 56 cases of mantle cell lymphoma. We identified recurrent mutations in ATM, CCND1, MLL2 and TP53. We further identified a number of novel genes recurrently mutated in patients with mantle cell lymphoma including RB1, WHSC1, POT1, and SMARCA4. We noted that mantle cell lymphomas have a distinct mutational profile compared to lymphomas from other B-cell stages. The ENCODE project has defined the [...]

A partir d'échantillons tumoraux prélevés sur plusieurs cohortes de patients chinois atteints d'un carcinome épidermoïde de l'œsophage, cette étude identifie un ensemble d'anomalies génomiques susceptibles de servir de cibles thérapeutiques

Genomic and molecular characterization of esophageal squamous cell carcinoma

Lin, De-Chen ; Hao, Jia-Jie ; Nagata, Yasunobu ; Xu, Liang ; Shang, Li ; Meng, Xuan ; Sato, Yusuke ; Okuno, Yusuke ; Varela, Ana Maria ; Ding, Ling-Wen ; Garg, Manoj ; Liu, Li-Zhen ; Yang, Henry ; Yin, Dong ; Shi, Zhi-Zhou ; Jiang, Yan-Yi ; Gu, Wen-Yue ; Gong, Ting ; Zhang, Yu ; Xu, Xin ; Kalid, Ori ; Shacham, Sharon ; Ogawa, Seishi ; Wang, Ming-Rong ; Koeffler, H. Phillip

Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to those already known (TP53, PIK3CA and NOTCH1). Further SCNV evaluation, immunohistochemistry and biological analysis [...]

Cet article passe en revue les travaux récents sur les divers rôles joués par la glycoprotéine SPARC dans la cancérogenèse

Molecular Mechanisms Underlying the Divergent Roles of SPARC in Human Carcinogenesis

Nagaraju, Ganji Purnachandra ; Dontula, Ranadheer ; Bassel, El-Rayes F. ; Lakka, Sajani S

Communication between the cell and its surrounding environment, consisting of proteinaceous (non-living material) and extracellular matrix (ECM), is important for bio-physiological and chemical signaling. This signaling results in a range of cellular activities, including cell division, adhesion, differentiation, invasion, migration, and angiogenesis. The ECM non-structural secretory glycoprotein called “secreted protein, acidic and rich in cysteine (SPARC), plays a significant role in altering [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence des mécanismes par lesquels, en régulant le compartiment des cellules souches de la prostate, les micro-ARNs de la famille miR-34 exercent, en association avec p53, une fonction de suppresseur de tumeurs

miR-34 Cooperates with p53 in Suppression of Prostate Cancer by Joint Regulation of Stem Cell Compartment

Cheng, Chieh-Yang ; Hwang, Chang-Il ; Corney, David C ; Flesken-Nikitin, Andrea ; Jiang, Longchang ; Öner, Gülfem Meryem ; Munroe, Robert J ; Schimenti, John C ; Hermeking, Heiko ; Nikitin, Alexander Yu

The miR-34 family was originally found to be a direct target of p53 and is a group of putative tumor suppressors. Surprisingly, mice lacking all mir-34 genes show no increase in cancer formation by 18 months of age, hence placing the physiological relevance of previous studies in doubt. Here, we report that mice with prostate epithelium-specific inactivation of mir-34 and p53 show expansion of the prostate stem cell compartment and develop early invasive adenocarcinomas and high-grade prostatic [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence des mécanismes par lesquels une surexpression du récepteur PPAR-d favorise le développement de tumeurs du côlon

Potentiation of Colon Cancer Susceptibility in Mice by Colonic Epithelial PPAR-δ/β Overexpression

Zuo, Xiangsheng ; Xu, Min ; Yu, Jiang ; Wu, Yuanqing ; Moussalli, Micheline J. ; Manyam, Ganiraju C. ; Lee, Sun Il ; Liang, Shoudan ; Gagea, Mihai ; Morris, Jeffrey S. ; Broaddus, Russell R. ; Shureiqi, Imad

Background : The nuclear receptor peroxisome proliferator-activated receptor-δ/β (PPAR-d) is upregulated in human colorectal cancers, but its role in colonic tumorigenesis remains controversial. Methods : We generated a novel mouse model of intestinally targeted PPAR-d overexpression to simulate PPAR-d upregulation in human colon carcinogenesis. Colon-specific PPAR-d overexpression was confirmed by real-time reverse transcription polymerase chain reaction, immunoblotting, and activity assays. [...]

Menée à l'aide de modèles murins de cancer du côlon, cette étude met en évidence des mécanismes par lesquels la signalisation p38

Dual Function of p38α MAPK in Colon Cancer: Suppression of Colitis-Associated Tumor Initiation but Requirement for Cancer Cell Survival

Gupta, Jalaj ; del Barco Barrantes, Ivan ; Igea, Ana ; Sakellariou, Stratigoula ; Pateras, Ioannis S ; Gorgoulis, Vassilis G ; Nebreda, Angel R

Colorectal cancer is frequently associated with chronic inflammation, with the intestinal epithelial barrier playing an important protective role against the infections and injuries that cause colitis. The p38α pathway regulates inflammatory responses but can also suppress tumor initiation in epithelial cells. We have found that p38α signaling has a dual function in colorectal tumorigenesis. On one side, p38α protects intestinal epithelial cells against colitis-associated colon cancer by [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels la signalisation S1PR1 favorise l'accumulation des lymphocytes T régulateurs dans les tumeurs

S1PR1 Is Crucial for Accumulation of Regulatory T Cells in Tumors via STAT3

Priceman, Saul J ; Shen, Shudan ; Wang, Lin ; Deng, Jiehui ; Yue, Chanyu ; Kujawski, Maciej ; Yu, Hua

S1PR1 signaling has been shown to restrain the number and function of regulatory T (Treg) cells in the periphery under physiological conditions and in colitis models, but its role in regulating tumor-associated T cells is unknown. Here, we show that S1PR1 signaling in T cells drives Treg accumulation in tumors, limits CD8+ T cell recruitment and activation, and promotes tumor growth. T-cell-intrinsic S1PR1 affects Treg cells, but not CD8+ T cells, as demonstrated by adoptive transfer models and [...]

Cet article passe en revue l'évolution de la recherche sur les cancers depuis 40 ans et pointe ses oscillations entre une vision réductionniste et une vision prenant en compte la complexité des processus

Coming Full Circle—From Endless Complexity to Simplicity and Back Again

Weinberg, Robert A.

Cell has celebrated the powers of reductionist molecular biology and its major successes for four decades. Those who have participated in cancer research during this period have witnessed wild fluctuations from times where endless inexplicable phenomenology reigned supreme to periods of reductionist triumphalism and, in recent years, to a move back to confronting the endless complexity of this disease.