Cet article analyse le rôle du vieillissement dans le développement des cancers

Cancer as a disease of old age: changing mutational and microenvironmental landscapes

Laconi, Ezio ; Marongiu, Fabio ; DeGregori, James

Why do we get cancer mostly when we are old? According to current paradigms, the answer is simple: mutations accumulate in our tissues throughout life, and some of these mutations contribute to cancers. Although mutations are necessary for cancer development, a number of studies shed light on roles for ageing and exposure-dependent changes in tissue landscapes that determine the impact of oncogenic mutations on cellular fitness, placing carcinogenesis into an evolutionary framework. Natural [...]

Menée à l'aide de modèles murins, cette étude met en évidence le rôle du catabolisme des acides aminés à chaîne ramifiée, induit par la transaminase BCAT2, dans le développement d'un adénocarcinome canalaire du pancréas

BCAT2-mediated BCAA catabolism is critical for development of pancreatic ductal adenocarcinoma

Li, Jin-Tao ; Yin, Miao ; Wang, Di ; Wang, Jian ; Lei, Ming-Zhu ; Zhang, Ye ; Liu, Ying ; Zhang, Lei ; Zou, Shao-Wu ; Hu, Li-Peng ; Zhang, Zhi-Gang ; Wang, Yi-Ping ; Wen, Wen-Yu ; Lu, Hao-Jie ; Chen, Zheng-Jun ; Su, Dan ; Lei, Qun-Ying

Branched-chain amino acid (BCAA) metabolism is potentially linked with development of pancreatic ductal adenocarcinoma (PDAC)1-4. BCAA transaminase 2 (BCAT2) was essential for the collateral lethality conferred by deletion of malic enzymes in PDAC and the BCAA–BCAT metabolic pathway contributed to non-small-cell lung carcinomas (NSCLCs) other than PDAC3,4. However, the underlying mechanism remains undefined. Here we reveal that BCAT2 is elevated in mouse models and in human PDAC. Furthermore, [...]

Menée à partir des données des projets "Genotype-Tissue Expression" et "The Cancer Genome Atlas", cette étude met en évidence le rôle de la polyadénylation alternative dans le développement d'un adénocarcinome canalaire du pancréas

Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma

Venkat, Swati ; Tisdale, Arwen A. ; Schwarz, Johann R. ; Alahmari, Abdulrahman A. ; Maurer, H. Carlo ; Olive, Kenneth P. ; Eng, Kevin H. ; Feigin, Michael E.

Alternative polyadenylation (APA) is a gene regulatory process that dictates mRNA 3'-UTR length, resulting in changes in mRNA stability and localization. APA is frequently disrupted in cancer and promotes tumorigenesis through altered expression of oncogenes and tumor suppressors. Pan-cancer analyses have revealed common APA events across the tumor landscape; however, little is known about tumor type-specific alterations that may uncover novel events and vulnerabilities. Here we integrate [...]

Menée à partir d'échantillons tumoraux prélevés sur 239 patients atteints d'un cancer de la prostate de stade localisé et traités par prostatectomie radicale, cette étude met en évidence un mécanisme par lequel des promoteurs alternatifs contrôlent le catabolisme des androgènes dépendants de l'UDP-Glucuronosyltransférase 2B17 et démontre l'influence de ce catabolisme sur la progression tumorale

Alternative promoters control UGT2B17-dependent androgen catabolism in prostate cancer and its influence on progression

Levesque, Eric ; Labriet, Adrien ; Hovington, Helène ; Allain, Éric P. ; Melo-Garcia, Luciana ; Rouleau, Michèle ; Brisson, Hervé ; Turcotte, Véronique ; Caron, Patrick ; Villeneuve, Lyne ; Leclercq, Mickaël ; Droit, Arnaud ; Audet-Walsh, Etienne ; Simonyan, David ; Fradet, Yves ; Lacombe, Louis ; Guillemette, Chantal

Background : Perturbation of the major UGT2B17-dependent androgen catabolism pathway has the potential to affect prostate cancer (PCa) progression. The objective was to evaluate UGT2B17 protein expression in primary tumours in relation to hormone levels, disease characteristics and cancer evolution. Methods : We conducted an analysis of a high-density prostate tumour tissue microarray consisting of 239 localised PCa cases treated by radical prostatectomy (RP). Cox proportional hazard ratio [...]

Menée à partir de cellules tumorales circulantes issues de patientes atteintes d'un cancer du sein et menée à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel la dérégulation de l'expression et de la traduction des protéines ribosomales favorise le développement de métastases

Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis

Ebright, Richard Y. ; Lee, Sooncheol ; Wittner, Ben S. ; Niederhoffer, Kira L. ; Nicholson, Benjamin T. ; Bardia, Aditya ; Truesdell, Samuel ; Wiley, Devon F. ; Wesley, Benjamin ; Li, Selena ; Mai, Andy ; Aceto, Nicola ; Vincent-Jordan, Nicole ; Szabolcs, Annamaria ; Chirn, Brian ; Kreuzer, Johannes ; Comaills, Valentine ; Kalinich, Mark ; Haas, Wilhelm ; Ting, David T. ; Toner, Mehmet ; Vasudevan, Shobha ; Haber, Daniel A. ; Maheswaran, Shyamala ; Micalizzi, Douglas S.

Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in breast cancer patient-derived CTCs to identify genes that promote their distant metastasis in mice. Genes coding for ribosomal proteins and regulators of translation were enriched in this screen. Overexpression of RPL15, which encodes a component of the large ribosomal subunit, increased metastatic growth [...]

Menée auprès de 188 patients atteints d'un cancer, cette étude met en évidence l'effet de l'obésité sur la consommation de glucose par les tumeurs mammaires et les tumeurs pulmonaires

The Impact of Obesity on Tumor Glucose Uptake in Breast and Lung Cancer

Leitner, Brooks P. ; Perry, Rachel J.

Obesity confers an increased incidence and poorer clinical prognosis in over ten cancer types. Paradoxically, obesity provides protection from poor outcomes in lung cancer. Mechanisms for the obesity-cancer links are not fully elucidated, with altered glucose metabolism being a promising candidate. Using 18F-Fluorodeoxyglucose positron-emission-tomography/computed-tomography images from The Cancer Imaging Archive, we explored the relationship between body mass index (BMI) and glucose metabolism [...]

Cet article passe en revue les études sur les caractéristiques biologiques des cancers d'origine primitive inconnue

Exploring the biological hallmarks of cancer of unknown primary: where do we stand today?

Rassy, Elie ; Assi, Tarek ; Pavlidis, Nicholas

Cancer of unknown primary (CUP) affects a small percentage of the general population. Nonetheless, a substantial number of these patients have a poor prognosis and consequently succumb to their illness within a year of diagnosis. The natural history of CUP is characterised by early metastasis from the unknown primary site, aggressive course and resistance to conventional chemotherapy. Unfortunately, the processes by which this orphan disease originates and progresses have not been fully [...]

Menée à partir de données de séquençage portant sur 2 658 tumeurs de 38 types différents, cette étude analyse les caractéristiques moléculaires de génomes mitochondriaux

Comprehensive molecular characterization of mitochondrial genomes in human cancers

Yuan, Yuan ; Ju, Young Seok ; Kim, Youngwook ; Li, Jun ; Wang, Yumeng ; Yoon, Christopher J. ; Yang, Yang ; Martincorena, Inigo ; Creighton, Chad J. ; Weinstein, John N. ; Xu, Yanxun ; Han, Leng ; Kim, Hyung-Lae ; Nakagawa, Hidewaki ; Park, Keunchil ; Campbell, Peter J. ; Liang, Han ; Pcawg Consortium

Mitochondria are essential cellular organelles that play critical roles in cancer. Here, as part of the International Cancer Genome Consortium/The Cancer Genome Atlas Pan-Cancer Analysis of Whole Genomes Consortium, which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we performed a multidimensional, integrated characterization of mitochondrial genomes and related RNA sequencing data. Our analysis presents the most definitive mutational landscape of [...]

Cet article présente le développement du "Angiosarcoma Project", une approche collaborative permettant aux patients américains et canadiens atteints d'un angiosarcome de partager à distance leurs informations cliniques et biologiques pour la recherche

The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research

Painter, Corrie A. ; Jain, Esha ; Tomson, Brett N. ; Dunphy, Michael ; Stoddard, Rachel E. ; Thomas, Beena S. ; Damon, Alyssa L. ; Shah, Shahrayz ; Kim, Dewey ; Gómez Tejeda Zañudo, Jorge ; Hornick, Jason L. ; Chen, Yen-Lin ; Merriam, Priscilla ; Raut, Chandrajit P. ; Demetri, George D. ; Van Tine, Brian A. ; Lander, Eric S. ; Golub, Todd R. ; Wagle, Nikhil

Despite rare cancers accounting for 25% of adult tumors1, they are difficult to study due to the low disease incidence and geographically dispersed patient populations, which has resulted in significant unmet clinical needs for patients with rare cancers. We assessed whether a patient-partnered research approach using online engagement can overcome these challenges, focusing on angiosarcoma, a sarcoma with an annual incidence of 300 cases in the United States. Here we describe the development [...]