Menée à partir de l'analyse du génome entier de 138 échantillons d'adénocarcinome pulmonaire, cette étude examine la corrélation entre réarrangements chromosomiques, oncogènes de fusion et mutations dans la carcinogenèse pulmonaire

Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma

Lee, Jake June-Koo ; Park, Seongyeol ; Park, Hansol ; Kim, Sehui ; Lee, Jongkeun ; Lee, Junehawk ; Youk, Jeonghwan ; Yi, Kijong ; An, Yohan ; Park, In Kyu ; Kang, Chang Hyun ; Chung, Doo Hyun ; Kim, Tae Min ; Jeon, Yoon Kyung ; Hong, Dongwan ; Park, Peter J. ; Ju, Young Seok ; Kim, Young Tae

Mutational processes giving rise to lung adenocarcinomas (LADCs) in non-smokers remain elusive. We analyzed 138 LADC whole genomes, including 83 cases with minimal contribution of smoking-associated mutational signature. Genomic rearrangements were not correlated with smoking-associated mutations and frequently served as driver events of smoking-signature-low LADCs. Complex genomic rearrangements, including chromothripsis and chromoplexy, generated 74% of known fusion oncogenes, including EML4- [...]

Menée à l'aide de modèles murins, cette étude démontre que des mutations du gène KRAS et du gène Lkb1 des cellules du canal pancréatique peuvent de façon synergique induire le développement d'une tumeur intracanalaire papillaire et mucineuse

Kras and Lkb1 mutations synergistically induce intraductal papillary mucinous neoplasm derived from pancreatic duct cells

Collet, Louis ; Ghurburrun, Elsa ; Meyers, Nora ; Assi, Mohamad ; Pirlot, Boris ; Leclercq, Isabelle A. ; Couvelard, Anne ; Komuta, Mina ; Cros, Jérôme ; Demetter, Pieter ; Lemaigre, Frédéric P. ; Borbath, Ivan ; Jacquemin, Patrick

Objective : Pancreatic cancer can arise from precursor lesions called intraductal papillary mucinous neoplasms (IPMN), which are characterised by cysts containing papillae and mucus-producing cells. The high frequency of KRAS mutations in IPMN and histological analyses suggest that oncogenic KRAS drives IPMN development from pancreatic duct cells. However, induction of Kras mutation in ductal cells is not sufficient to generate IPMN, and formal proof of a ductal origin of IPMN is still missing. [...]

Menée in vitro et à l'aide d'un modèle murin de carcinome hépatocellulaire, cette étude met en évidence un mécanisme par lequel l'interaction entre la cytidine désaminase APOBEC3B et le complexe protéique PRC2 favorise la progression de la tumeur en modifiant son micro-environnement

APOBEC3B interaction with PRC2 modulates microenvironment to promote HCC progression

Wang, Duowei ; Li, Xianjing ; Li, Jiani ; Lu, Yuan ; Zhao, Sen ; Tang, Xinying ; Chen, Xin ; Li, Jiaying ; Zheng, Yan ; Li, Shuran ; Sun, Rui ; Yan, Ming ; Yu, Decai ; Cao, Guangwen ; Yang, Yong

Objective : APOBEC3B (A3B), a cytidine deaminase acting as a contributor to the APOBEC mutation pattern in many kinds of tumours, is upregulated in patients with hepatocellular carcinoma (HCC). However, APOBEC mutation patterns are absent in HCC. The mechanism of how A3B affects HCC progression remains elusive. Design : A3B promoter luciferase reporter and other techniques were applied to elucidate mechanisms of A3B upregulation in HCC. A3B overexpression and knockdown cell models, [...]

Cet article analyse la valeur prédictive des neutrophiles associés aux tumeurs, leur rôle dans la progression tumorale et leurs implications thérapeutiques

Tumour-associated neutrophils in patients with cancer

Shaul, Merav E. ; Fridlender, Zvi G.

The role and importance of neutrophils in cancer has become increasingly apparent over the past decade. Neutrophils accumulate in the peripheral blood of patients with cancer, especially in those with advanced-stage disease, and a high circulating neutrophil-to-lymphocyte ratio is a robust biomarker of poor clinical outcome in various cancers. To date, most studies investigating the role of neutrophils in cancer have involved animal models or investigated the function of circulating human [...]

Menée à l'aide de cellules leucémiques provenant de 107 patients atteints d'une leucémie chronique lymphocytaire, cette étude analyse la corrélation entre l'évolution des caractéristiques génétiques des cellules cancéreuses et l'évolution de la croissance tumorale

Growth dynamics in naturally progressing chronic lymphocytic leukaemia

Gruber, Michaela ; Bozic, Ivana ; Leshchiner, Ignaty ; Livitz, Dimitri ; Stevenson, Kristen ; Rassenti, Laura ; Rosebrock, Daniel ; Taylor-Weiner, Amaro ; Olive, Oriol ; Goyetche, Reaha ; Fernandes, Stacey M. ; Sun, Jing ; Stewart, Chip ; Wong, Alicia ; Cibulskis, Carrie ; Zhang, Wandi ; Reiter, Johannes G. ; Gerold, Jeffrey M. ; Gribben, John G. ; Rai, Kanti R. ; Keating, Michael J. ; Brown, Jennifer R. ; Neuberg, Donna ; Kipps, Thomas J. ; Nowak, Martin A. ; Getz, Gad ; Wu, Catherine J.

How the genomic features of a patient’s cancer relate to individual disease kinetics remains poorly understood. Here we used the indolent growth dynamics of chronic lymphocytic leukaemia (CLL) to analyse the growth rates and corresponding genomic patterns of leukaemia cells from 107 patients with CLL, spanning decades-long disease courses. We found that CLL commonly demonstrates not only exponential expansion but also logistic growth, which is sigmoidal and reaches a certain steady-state level. [...]

Menée in vitro et à l'aide d'un modèle murin de cancer mammaire, cette étude met en évidence un mécanisme par lequel la ligase SCFFBXO22, en agissant sur l'oncoprotéine HDM2, favorise la dégradation de cette dernière et régule les processus invasif et métastatique des cellules cancéreuses

SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis

Bai, Jin ; Wu, Kenneth ; Cao, Meng-Han ; Yang, Yingying ; Pan, Yu ; Liu, Hui ; He, Yizhou ; Itahana, Yoko ; Huang, Lan ; Zheng, Jun-Nian ; Pan, Zhen-Qiang

Human homolog of mouse double minute 2 (HDM2) is an oncogene frequently overexpressed in cancers with poor prognosis, but mechanisms of controlling its abundance remain elusive. In an unbiased biochemical search, we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets [...]

Menée sur quatre lignées cellulaires de cancer colorectal, cette étude met en évidence une modification du programme transcriptionnel et du métabolisme des cellules cancéreuses présentant la mutation oncogène KRAS G13D

Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRASG13D mutation

Charitou, Theodosia ; Srihari, Sriganesh ; Lynn, Miriam A. ; Jarboui, Mohamed-Ali ; Fasterius, Erik ; Moldovan, Max ; Shirasawa, Senji ; Tsunoda, Toshiyuki ; Ueffing, Marius ; Xie, Jianling ; Xin, Jin ; Wang, Xuemin ; Proud, Christopher G. ; Boldt, Karsten ; Al-Khalili Szigyarto, Cristina ; Kolch, Walter ; Lynn, David J.

Background : Activating mutations in KRAS frequently occur in colorectal cancer (CRC) patients, leading to resistance to EGFR-targeted therapies. Methods : To better understand the cellular reprogramming which occurs in mutant KRAS cells, we have undertaken a systems-level analysis of four CRC cell lines which express either wild type (wt) KRAS or the oncogenic KRASG13D allele (mtKRAS). Results : RNAseq revealed that genes involved in ribosome biogenesis, mRNA translation and metabolism were [...]