A partir d'échantillons tumoraux prélevés sur 66 patients afro-américains atteints d'un cancer colorectal, cette étude identifie des mutations dans un panel de 15 gènes en association avec un pronostic défavorable dans cette population

Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers

Wang, Zhenghe ; Li, Li ; Guda, Kishore ; Chen, Zhengyi ; Barnholtz-Sloan, Jill ; Park, Young Soo ; Markowitz, Sanford D. ; Willis, Joseph

African Americans have the highest incidence and mortality from colorectal cancer (CRC) of any US racial group. We recently described a panel of 15 genes that are statistically significantly more likely to be mutated in CRCs from African Americans than in Caucasians (AA-CRC genes). The current study investigated the outcomes associated with these mutations in African American CRCs (AA-CRCs). In a cohort of 66 patients with stage I-III CRCs, eight of 27 CRCs with AA-CRC gene mutations (Mut+) [...]

A partir d'une analyse génomique de 1 000 cellules issues de tumeurs prélevées sur 12 patientes atteintes d'un cancer du sein triplement négatif, cette étude remet en cause le paradigme d'une évolution graduelle de la tumeur en suggérant que la plupart des anomalies de nombres de copies de gènes sont acquises précocement

Punctuated copy number evolution and clonal stasis in triple-negative breast cancer

Gao, Ruli ; Davis, Alexander ; McDonald, Thomas O. ; Sei, Emi ; Shi, Xiuqing ; Wang, Yong ; Tsai, Pei-Ching ; Casasent, Anna ; Waters, Jill ; Zhang, Hong ; Meric-Bernstam, Funda ; Michor, Franziska ; Navin, Nicholas E.

Aneuploidy is a hallmark of breast cancer; however, knowledge of how these complex genomic rearrangements evolve during tumorigenesis is limited. In this study, we developed a highly multiplexed single-nucleus sequencing method to investigate copy number evolution in patients with triple-negative breast cancer. We sequenced 1,000 single cells from tumors in 12 patients and identified 1-3 major clonal subpopulations in each tumor that shared a common evolutionary lineage. For each tumor, we also [...]

Menée sur des poissons-zèbres, cette étude met en évidence des mécanismes par lesquels un déficit d'expression du gène de la sélénoprotéine H augmente le risque de développement d'une tumeur gastrointestinale

Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis

Cox, Andrew G. ; Tsomides, Allison ; Kim, Andrew J. ; Saunders, Diane ; Hwang, Katie L. ; Evason, Kimberley J. ; Heidel, Jerry ; Brown, Kristin K. ; Yuan, Min ; Lien, Evan C. ; Lee, Byung Cheon ; Nissim, Sahar ; Dickinson, Bryan ; Chhangawala, Sagar ; Chang, Christopher J. ; Asara, John M. ; Houvras, Yariv ; Gladyshev, Vadim N. ; Goessling, Wolfram

Selenium, an essential micronutrient known for its cancer prevention properties, is incorporated into a class of selenocysteine-containing proteins (selenoproteins). Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LC-MS/MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of [...]

A partir des bases de données METAFABRIC et TGCA, puis menée sur des lignées cellulaires de cancer du sein, cette étude identifie des mutations somatiques et constitutionnelles dans un ensemble d'éléments régulant l'expression du gène ESR1

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer

Bailey, Swneke D. ; Desai, Kinjal ; Kron, Ken J. ; Mazrooei, Parisa ; Sinnott-Armstrong, Nicholas A. ; Treloar, Aislinn E. ; Dowar, Mark ; Thu, Kelsie L. ; Cescon, David W. ; Silvester, Jennifer ; Yang, S. Y. Cindy ; Wu, Xue ; Pezo, Rossanna C. ; Haibe-Kains, Benjamin ; Mak, Tak W. ; Bedard, Philippe L. ; Pugh, Trevor J. ; Sallari, Richard C. ; Lupien, Mathieu

Sustained expression of the estrogen receptor-

A partir de 995 échantillons tumoraux prélevés sur des patientes atteintes d'un cancer du sein, cette étude identifie un ensemble de longs ARNs non codant impliqués dans la cancérogenèse

Portraying breast cancers with long noncoding RNAs

Van Grembergen, Olivier ; Bizet, Martin ; de Bony, Eric J. ; Calonne, Emilie ; Putmans, Pascale ; Brohee, Sylvain ; Olsen, Catharina ; Guo, Mingzhou ; Bontempi, Gianluca ; Sotiriou, Christos ; Defrance, Matthieu ; Fuks, Francois

Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer development, but this role is not yet clear. We performed a genome-wide transcriptional survey to explore the lncRNA landscape across 995 breast tissue samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast tumors, as compared to normal samples. Unsupervised hierarchical clustering of breast tumors on the basis of their lncRNAs revealed four breast cancer subgroups that correlate tightly [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels des péricytes vasculaires du microenvironnement tumoral favorisent les processus invasif et métastatique

Pericyte–fibroblast transition promotes tumor growth and metastasis

Hosaka, Kayoko ; Yang, Yunlong ; Seki, Takahiro ; Fischer, Carina ; Dubey, Olivier ; Fredlund, Erik ; Hartman, Johan ; Religa, Piotr ; Morikawa, Hiromasa ; Ishii, Yoko ; Sasahara, Masakiyo ; Larsson, Ola ; Cossu, Giulio ; Cao, Renhai ; Lim, Sharon ; Cao, Yihai

Vascular pericytes, an important cellular component in the tumor microenvironment, are often associated with tumor vasculatures, and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte–fibroblast transition (PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that PDGF-BB-PDGFRβ signaling promotes PFT both in vitro and in in vivo tumors. Genome-wide expression [...]

Cet article passe en revue les travaux récents sur le rôle joué par l'autophagie dans la régulation du processus métastatique

Autophagy in cancer metastasis

Mowers, E. E. ; Sharifi, M. N. ; Macleod, K. F.

Autophagy is a highly conserved self-degradative process that has a key role in cellular stress responses and survival. Recent work has begun to explore the function of autophagy in cancer metastasis, which is of particular interest given the dearth of effective therapeutic options for metastatic disease. Autophagy is induced upon progression of various human cancers to metastasis and together with data from genetically engineered mice and experimental metastasis models, a role for autophagy at [...]

Menée in vitro et in vivo sur des modèles de mélanome, cette étude met en évidence le rôle joué par l'expression du gène PGC1alpha dans le processus métastatique

A PGC1alpha-mediated transcriptional axis suppresses melanoma metastasis

Luo, Chi ; Lim, Ji-Hong ; Lee, Yoonjin ; Granter, Scott R. ; Thomas, Ajith ; Vazquez, Francisca ; Widlund, Hans R. ; Puigserver, Pere

Melanoma is the deadliest form of commonly encountered skin cancer because of its rapid progression towards metastasis. Although metabolic reprogramming is tightly associated with tumour progression, the effect of metabolic regulatory circuits on metastatic processes is poorly understood. PGC1

Menée sur des lignées cellulaires de cancer colorectal et à l'aide de xénogreffes sur des poissons-zèbres, cette étude met en évidence des mécanismes par lesquels le facteur de transcription MYC-nick favorise le processus métastatique

MYC-nick promotes cell migration by inducing fascin expression and Cdc42 activation

Anderson, Sarah ; Poudel, Kumud Raj ; Roh-Johnson, Minna ; Brabletz, Thomas ; Yu, Ming ; Borenstein-Auerbach, Nofit ; Grady, William N. ; Bai, Jihong ; Moens, Cecilia B. ; Eisenman, Robert N. ; Conacci-Sorrell, Maralice

MYC-nick is a cytoplasmic, transcriptionally inactive member of the MYC oncoprotein family, generated by a proteolytic cleavage of full-length MYC. MYC-nick promotes migration and survival of cells in response to chemotherapeutic agents or withdrawal of glucose. Here we report that MYC-nick is abundant in colonic and intestinal tumors derived from mouse models with mutations in the Wnt, TGF-β, and PI3K pathways. Moreover, MYC-nick is elevated in colon cancer cells deleted for FBWX7, which [...]

Menée sur des lignées cellulaires, cette étude met en évidence des mécanismes épigénétiques par lesquels, en induisant une accumulation de fumarate dans les cellules cancéreuses, une perte d'expression du gène de la fumarate hydratase induit une transition épithélio-mésenchymateuse et favorise le processus métastatique d'un cancer du rein

Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition

Sciacovelli, Marco ; Gonçalves, Emanuel ; Johnson, Timothy Isaac ; Zecchini, Vincent Roberto ; da Costa, Ana Sofia Henriques ; Gaude, Edoardo ; Drubbel, Alizee Vercauteren ; Theobald, Sebastian Julian ; Abbo, Sandra Riekje ; Tran, Maxine Gia Binh ; Rajeeve, Vinothini ; Cardaci, Simone ; Foster, Sarah ; Yun, Haiyang ; Cutillas, Pedro ; Warren, Anne ; Gnanapragasam, Vincent ; Gottlieb, Eyal ; Franze, Kristian ; Huntly, Brian ; Maher, Eamonn Richard ; Maxwell, Patrick Henry ; Saez-Rodriguez, Julio ; Frezza, Christian

Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a bona fide oncometabolite. Fumarate has been shown to inhibit

Cet article présente les recommandations d'un groupe d'experts internationaux en matière de méthodes de validation des anticorps utilisés en recherche

A proposal for validation of antibodies

Uhlén, Mathias ; Bandrowski, Anita ; Carr, Steven ; Edwards, Aled ; Ellenberg, Jan ; Lundberg, Emma ; Rimm, David L. ; Rodriguez, Henry ; Hiltke, Tara ; Snyder, Michael ; Yamamoto, Tadashi

We convened an ad hoc International Working Group for Antibody Validation in order to formulate the best approaches for validating antibodies used in common research applications and to provide guidelines that ensure antibody reproducibility. We recommend five conceptual 'pillars' for antibody validation to be used in an application-specific manner.

A partir d'une analyse de l'ADN, cette étude montre qu'une lignée cellulaire de gliome couramment utilisée en recherche (U87MG) ne peut pas être dérivée de la tumeur d'origine à laquelle elle était jusqu'à présent reliée

Origin of the U87MG glioma cell line: Good news and bad news

Allen, Marie ; Bjerke, Mia ; Edlund, Hanna ; Nelander, Sven ; Westermark, Bengt

A cell line commonly used for research on gliomas is found to be different from the original tumor from which it was derived. The authors, whose laboratory developed the cell line almost 50 years ago, compared the genetics of this line (obtained from ATCC) with those of the original tumor. They report that the DNA profile of the current cell line differs from that of the original cells but that it is likely to be a human glioblastoma cell line with unknown origins. This misidentification of a [...]