Menée à l'aide de nanofils en silicium permettant d'introduire de petits ARNs interférents dans des cellules de leucémie lymphocytaire chronique, cette étude met en évidence le rôle joué par des mutations somatiques de gènes de la voie de signalisation Wnt dans le développement de la maladie

Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL

Wang, Lili ; Shalek, Alex K. ; Lawrence, Mike ; Ding, Ruihua ; Gaublomme, Jellert T. ; Pochet, Nathalie ; Stojanov, Petar ; Sougnez, Carrie ; Shukla, Sachet A. ; Stevenson, Kristen E. ; Zhang, Wandi ; Wong, Jessica ; Sievers, Quinlan L. ; MacDonald, Bryan T. ; Vartanov, Alexander R. ; Goldstein, Natalie R. ; Neuberg, Donna ; He, Xi ; Lander, Eric ; Hacohen, Nir ; Regev, Aviv ; Getz, Gad ; Brown, Jennifer R. ; Park, Hongkun ; Wu, Catherine J.

One major goal of cancer genome sequencing is to identify key genes and pathways that drive tumor pathogenesis. While many studies have identified candidate driver genes based on recurrence of mutations in individual genes, subsets of genes with non-recurrent mutations may also be defined as putative drivers if they affect a single biological pathway. In this fashion, we previously identified Wnt signaling as significantly mutated through large-scale massively-parallel DNA sequencing of chronic [...]

Menée sur des échantillons prélevés sur 587 patients atteints d'une leucémie lymphocytaire chronique, cette étude identifie des mutations des gènes MYD88 et du récepteur Toll-like en association avec un pronostic favorable chez les patients d'âge inférieur à 50 ans

Mutations in the Toll-like receptor/MYD88 pathway in chronic lymphocytic leukemia identify a subset of young patients with favorable outcome

Martinez-Trillos, Alejandra ; Pinyol, Magda ; Navarro, Alba ; Aymerich, Marta ; Jares, Pedro ; Juan, Manel ; Rozman, Maria ; Colomer, Dolors ; Delgado, Julio ; Giné, Eva ; González-Díaz, Marcos ; Hernández-Rivas, Jesús M. ; Colado, Enrique ; Rayón, Consolación ; Payer, Angel R. ; Terol, María José ; Navarro, Blanca ; Quesada, Victor ; Puente, Xose S. ; Rozman, Ciril ; López-Otín, Carlos ; Campo, Elias ; Lopez-Guillermo, Armando ; Villamor, Neus

Mutations in Toll-like receptor and MYD88 genes (TLR/MYD88) have been found in chronic lymphocytic leukemia (CLL) at low frequency. We analyzed the incidence, clinicobiological characteristics and outcome of patients with mutations in TLR/MYD88 in 587 CLL patients by either whole-exome or Sanger sequencing. Twenty-three patients (3.9%) had mutations, 19 in MYD88 (one with concurrent IRAK1 mutation), 2 TLR2 (one with concomitant TLR6 mutation), 1 IRAK1 and 1 TLR5. No mutations were found in [...]

Menée initialement sur 20 échantillons tumoraux prélevés sur des patients atteints d'un rhabdomyosarcome, puis sur 93 échantillons complémentaires, cette étude identifie une mutation du gène MYOD1 associée à un pronostic défavorable chez les patients atteints d'un rhabdomyosarcome embryonnaire présentant des mutations de gènes de la voie de signalisation PI3K-AKT

A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations

Kohsaka, Shinji ; Shukla, Neerav ; Ameur, Nabahet ; Ito, Tatsuo ; Ng, Charlotte K. Y. ; Wang, Lu ; Lim, Diana ; Marchetti, Angela ; Viale, Agnes ; Pirun, Mono ; Socci, Nicholas D. ; Qin, Li-Xuan ; Sciot, Raf ; Bridge, Julia ; Singer, Samuel ; Meyers, Paul ; Wexler, Leonard H. ; Barr, Frederic G. ; Dogan, Snjezana ; Fletcher, Jonathan A. ; Reis-Filho, Jorge S. ; Ladanyi, Marc

Rhabdomyosarcoma, a cancer of skeletal muscle lineage, is the most common soft-tissue sarcoma in children. Major subtypes of rhabdomyosarcoma include alveolar (ARMS) and embryonal (ERMS) tumors. Whereas ARMS tumors typically contain translocations generating PAX3-FOXO1 or PAX7-FOXO1 fusions that block terminal myogenic differentiation, no functionally comparable genetic event has been found in ERMS tumors. Here we report the discovery, through whole-exome sequencing, of a recurrent somatic [...]

Menée sur des échantillons tumoraux prélevés sur 354 patients atteints d'un gliome, puis in vitro, cette étude met en évidence des mécanismes par lesquels le gène IDH1, lorsqu'il est muté, inhibe la signalisation PI3K/Akt

Mutant IDH1 inhibits PI3K/Akt signaling in human glioma

Birner, Peter ; Pusch, Stefan ; Christov, Christo ; Mihaylova, Stiliana ; Toumangelova-Uzeir, Kalina ; Natchev, Sevdalin ; Schoppmann, Sebastian F. ; Tchorbanov, Andrey ; Streubel, Berthold ; Tuettenberg, Jochen ; Guentchev, Marin

BACKGROUND : Recently, isocitrate dehydrogenase 1 (IDH1) was identified as a major participant in glioma pathogenesis. At present, the enzymatic activity of the protein has been the main topic in investigating its physiological function, but its signaling pathway allocation was unsuccessful. Interestingly, proteins regulated by phosphoinositide 3-kinase (PI3K)/Akt signaling, are among the top downregulated genes in gliomas associated with high percentage of IDH1 and IDH2 mutations. The aim of [...]

Menée sur 14 échantillons tumoraux prélevés sur des patients atteints d'un cancer de la vessie de différents grades et stades, cette étude de séquençage du génome entier identifie un ensemble de mutations somatiques, notamment dans le gène CDKN1A

Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden

Cazier, J. B. ; Rao, S. R. ; McLean, C. M. ; Walker, A. L. ; Wright, B. J. ; Jaeger, E. E. M. ; Kartsonaki, C. ; Marsden, L. ; Yau, C. ; Camps, C. ; Kaisaki, P. ; The Oxford-Illumina, W. G. S. Consortium ; Taylor, J. ; Catto, J. W. ; Tomlinson, I. P. M. ; Kiltie, A. E. ; Hamdy, F. C.

Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence des mécanismes par lesquels, en étant exprimée de façon préférentielle dans le réseau vasculaire tumoral, la protéine FasL régule l'infiltration des lymphocytes T à l'intérieur des tumeurs

Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors

Motz, Gregory T. ; Santoro, Stephen P. ; Wang, Li-Ping ; Garrabrant, Tom ; Lastra, Ricardo R. ; Hagemann, Ian S. ; Lal, Priti ; Feldman, Michael D. ; Benencia, Fabian ; Coukos, George

We describe a new mechanism regulating the tumor endothelial barrier and T cell infiltration into tumors. We detected selective expression of the death mediator Fas ligand (FasL, also called CD95L) in the vasculature of human and mouse solid tumors but not in normal vasculature. In these tumors, FasL expression was associated with scarce CD8+ infiltration and a predominance of FoxP3+ T regulatory (Treg) cells. Tumor-derived vascular endothelial growth factor A (VEGF-A), interleukin 10 (IL-10) [...]

A partir de données portant sur quelque 5 000 génomes tumoraux, puis menée in vitro, cette étude met en évidence des mécanismes par lesquels, en régulant l'expression des cyclines D et E, la protéine PARK2 exerce une fonction de suppresseur de tumeurs

Pan-cancer genetic analysis identifies PARK2 as a master regulator of G1/S cyclins

Gong, Yongxing ; Zack, Travis Ian ; Morris, Luc G. T. ; Lin, Kan ; Hukkelhoven, Ellen ; Raheja, Radhika ; Tan, I. Li ; Turcan, Sevin ; Veeriah, Selvaraju ; Meng, Shasha ; Viale, Agnes ; Schumacher, Steven E. ; Palmedo, Perry ; Beroukhim, Rameen ; Chan, Timothy A.

Coordinate control of different classes of cyclins is fundamentally important for cell cycle regulation and tumor suppression, yet the underlying mechanisms are incompletely understood. Here we show that the PARK2 tumor suppressor mediates this coordination. The PARK2 E3 ubiquitin ligase coordinately controls the stability of both cyclin D and cyclin E. Analysis of approximately 5,000 tumor genomes shows that PARK2 is a very frequently deleted gene in human cancer and uncovers a striking [...]

Menée in vitro, cette étude met en évidence le rôle joué par le micro-ARN miR-542-3p dans la régulation de l'expression du gène suppresseur de tumeurs p53

p53 is positively regulated by miR-542-3p

Wang, Yemin ; Huang, Jen-Wei ; Castella, Maria ; Huntsman, David George ; Taniguchi, Toshiyasu

The tumor suppressor p53 and microRNAs (miRNAs) are linked through a complex network. Several miRNAs modulate p53 expression, while p53 regulates the transcription and/or biogenesis of several other miRNAs. Here we report the development of a cell-based assay used with a library of human miRNA mimics in a high-throughput screen for miRNAs that modulate p53 expression. Overexpression of miR-542-3p in cancer cells elevated p53 expression, stimulated the expression of p53 targets and inhibited [...]

Menée à l'aide d'un modèle murin transgénique, cette étude met en évidence des mécanismes par lesquels, en régulant de façon spécifique l'expression du gène PTEN, le microenvironnement de certains tissus est susceptible d'induire une hétérogénéité dans les populations cellulaires de leucémie lymphoblastique aiguë

PTEN action in leukaemia dictated by the tissue microenvironment

Miething, Cornelius ; Scuoppo, Claudio ; Bosbach, Benedikt ; Appelmann, Iris ; Nakitandwe, Joy ; Ma, Jing ; Wu, Gang ; Lintault, Laura ; Auer, Martina ; Premsrirut, Prem K. ; Teruya-Feldstein, Julie ; Hicks, James ; Benveniste, Helene ; Speicher, Michael R. ; Downing, James R. ; Lowe, Scott W.

PTEN encodes a lipid phosphatase that is underexpressed in many cancers owing to deletions, mutations or gene silencing. PTEN dephosphorylates phosphatidylinositol -triphosphate, thereby opposing the activity of class I phosphatidylinositol 3-kinases that mediate growth- and survival-factor signalling through phosphatidylinositol 3-kinase effectors such as AKT and mTOR2. To determine whether continued PTEN inactivation is required to maintain malignancy, here we generate an RNA [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels le micro-ARN miR-615-5p exerce une fonction de suppresseur de tumeurs

miR-615-5p is epigenetically inactivated and functions as a tumor suppressor in pancreatic ductal adenocarcinoma

Gao, W. ; Gu, Y. ; Li, Z. ; Cai, H. ; Peng, Q. ; Tu, M. ; Kondo, Y. ; Shinjo, K. ; Zhu, Y. ; Zhang, J. ; Sekido, Y. ; Han, B. ; Qian, Z. ; Miao, Y.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis. Although microRNA (miRNA) transcripts have a crucial role in carcinogenesis and development, little information is known regarding the aberrant DNA methylation of miRNAs in PDAC. Using methylated DNA immunoprecipitation-chip analysis, we found that miR-615-5p was hypermethylated in its putative promoter region, which silenced its expression in PDAC cell lines. In addition, the overexpression of miR-615-5p [...]

Menée à partir d'échantillons tumoraux prélevés sur des patients atteints d'une tumeur stromale gastrointestinale, d'un rhabdomyosarcome ou d'un léiomyosarcome, puis sur des lignées cellulaires, cette étude met en évidence des mécanismes par lesquels la dystrophine exerce une fonction de suppresseur de tumeurs

Dystrophin is a tumor suppressor in human cancers with myogenic programs

Wang, Yuexiang ; Marino-Enriquez, Adrian ; Bennett, Richard R. ; Zhu, Meijun ; Shen, Yiping ; Eilers, Grant ; Lee, Jen-Chieh ; Henze, Joern ; Fletcher, Benjamin S. ; Gu, Zhizhan ; Fox, Edward A. ; Antonescu, Cristina R. ; Fletcher, Christopher D. M. ; Guo, Xiangqian ; Raut, Chandrajit P. ; Demetri, George D. ; van de Rijn, Matt ; Ordog, Tamas ; Kunkel, Louis M. ; Fletcher, Jonathan A.

Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS), feature myogenic differentiation. Here we report that intragenic deletion of the dystrophin-encoding and muscular dystrophy–associated DMD gene is a frequent mechanism by which myogenic tumors progress to high-grade, lethal sarcomas. Dystrophin is expressed in the non-neoplastic and benign counterparts of GIST, RMS and LMS tumors, and DMD deletions inactivate [...]

Menée in vitro, cette étude met en évidence des mécanismes permettant de rendre compte du rôle joué par des mutations du gène BRCA1 dans l'instabilité génomique et la prédisposition à un cancer du sein ou de l'ovaire

BRCA1 controls homologous recombination at Tus/Ter-stalled mammalian replication forks

Willis, Nicholas A. ; Chandramouly, Gurushankar ; Huang, Bin ; Kwok, Amy ; Follonier, Cindy ; Deng, Chuxia ; Scully, Ralph

Replication fork stalling can promote genomic instability, predisposing to cancer and other diseases. Stalled replication forks may be processed by sister chromatid recombination (SCR), generating error-free or error-prone homologous recombination (HR) outcomes. In mammalian cells, a long-standing hypothesis proposes that the major hereditary breast/ovarian cancer predisposition gene products, BRCA1 and BRCA2, control HR/SCR at stalled replication forks9. Although BRCA1 and BRCA2 affect [...]

Menée sur des lignées cellulaires de cancer du sein, cette étude met en évidence des mécanismes par lesquels, en interaction avec MYC, la protéine MTBP favorise la transformation maligne

Oncogenic protein MTBP interacts with MYC to promote tumorigenesis

Grieb, Brian C ; Gramling, Mark W ; Arrate, Maria Pia ; Chen, Xi ; Beauparlant, Stephen L ; Haines, Dale S ; Xiao, Hua ; Eischen, Christine M.

Despite its involvement in most human cancers, MYC continues to pose a challenge as a readily tractable therapeutic target. Here we identify the MYC transcriptional cofactors TIP48 and TIP49 and MYC as novel binding partners of MTBP, a functionally undefined protein that we show is oncogenic and overexpressed in many human cancers. MTBP associated with MYC at promoters and increased MYC-mediated transcription, proliferation, neoplastic transformation and tumor development. In breast cancer [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels la bêta-caténine favorise le processus métastatique d'un cancer gastrique

Cooperativity of E-cadherin and Smad4 Loss to Promote Diffuse-type Gastric Adenocarcinoma and Metastasis

Park, Jun Won ; Jang, Seok Hoon ; Park, Dong Min ; Lim, Na Jung ; Deng, Chuxia ; Kim, Dae Yong ; Green, Jeffrey E. ; Kim, Hark Kyun

Loss of E-cadherin (CDH1), Smad4 and p53 have all been shown to play an integral role in gastric, intestinal and breast cancer formation. Compound conditional knockout mice for Smad4, p53, and Ecadherin were generated to define and compare the roles of these genes in gastric, intestinal and breast cancer development by crossing with Pdx-1-Cre, Villin-Cre and MMTV-Cre transgenic mice. Interestingly, gastric adenocarcinoma was significantly more frequent in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, via le complexe

TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives

Kato, Takuya ; Enomoto, Atsushi ; Watanabe, Takashi ; Haga, Hisashi ; Ishida, Sumire ; Kondo, Yuji ; Furukawa, Koichi ; Urano, Takeshi ; Mii, Shinji ; Weng, Liang ; Ishida-Takagishi, Maki ; Asai, Masato ; Asai, Naoya ; Kaibuchi, Kozo ; Murakumo, Yoshiki ; Takahashi, Masahide

For collective invasion, cancer cells form cohesive groups comprised of leading cells (LCs) at the forefront and following cells (FCs) at the rear. However, the molecular mechanisms that define LCs and FCs remain elusive. Here, we demonstrated that LCs, but not FCs, upregulated the expression of integrin

Menée in vitro et in vivo, cette étude met en évidence le rôle joué par l'interleukine 18 dans la progression d'une leucémie aiguë T

Interleukin-18 produced by bone marrow-derived stromal cells supports T-cell acute leukaemia progression

Uzan, Benjamin ; Poglio, Sandrine ; Gerby, Bastien ; Wu, Ching-Lien ; Gross, Julia ; Armstrong, Florence ; Calvo, Julien ; Cahu, Xavier ; Deswarte, Caroline ; Dumont, Florent ; Passaro, Diana ; Besnard-Guérin, Corinne ; Leblanc, Thierry ; Baruchel, André ; Landman-Parker, Judith ; Ballerini, Paola ; Baud, Veronique ; Ghysdael, Jacques ; Baleydier, Frederic ; Porteu, Françoise ; Pflumio, Francoise

Development of novel therapies is critical for T-cell acute leukaemia (T-ALL). Here, we investigated the effect of inhibiting the MAPK/MEK/ERK pathway on T-ALL cell growth. Unexpectedly, MEK inhibitors (MEKi) enhanced growth of 70% of human T-ALL cell samples cultured on stromal cells independently of NOTCH activation and maintained their ability to propagate in vivo. Similar results were obtained when T-ALL cells were cultured with ERK1/2-knockdown stromal cells or with conditioned medium from [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en s'exprimant sur la surface des cellules de mélanome, une protéine (LSCEtin) favorise l'échappement à la réponse immune et la progression tumorale

LSECtin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T cell responses

Tang, Li ; Xu, Feng ; Liu, Jing ; Liu, Di ; Liu, Biao ; Wang, Min ; Hu, Zhiyuan ; Du, Xuemei ; He, Fuchu

Co-inhibitory molecules of T cell immune responses have received considerable attention for their successful clinical effects during immunotherapy for the treatment of multiple cancers. LSECtin, a cell-surface member of the C-type lectin DC-SIGN family, has been shown to inhibit T cell responses and viral clearance in the liver. However, its role in antitumor immunity and tumor growth remains unclear. Herein, we detected LSECtin expression in approximately 50% of melanoma samples in a human [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels la sirtuine Sirt7 favorise le développement et la progression d'un cancer colorectal

Overexpression of Sirt7 exhibits oncogenic property and serves as a prognostic factor in colorectal cancer

Yu, Hongyan ; Ye, Wen ; Wu, Jiangxue ; Meng, Xiangqi ; Liu, Ran-yi ; Ying, Xiaofang ; Zhou, Yi ; Wang, Hui ; Pan, Changchuan ; Huang, Wenlin

Purpose: Sirtuins play an important role in cancer development. Sirt7, as a member of this family, is frequently overexpressed in certain carcinomas, but the oncogenic mechanism is seldom reported. In this study, Sirt7 was characterized for its role in colorectal cancer (CRC) aggressiveness and underlying molecular mechanisms. Experimental Design: Quantitative PCR, Western blotting and immunohistochemistry were performed to study Sirt7 expression in a cohort of CRC tissues and non-tumor tissues [...]

Menée à l'aide de modèles murins génétiquement modifiés, cette étude met en évidence des mécanismes par lesquels, en régulant la signalisation c-MET, la protéine SPSB1 favorise la récidive d'un cancer du sein

SPSB1 Promotes Breast Cancer Recurrence by Potentiating c-MET Signaling

Feng, Yi ; Pan, Tien-chi ; Pant, Dhruv K ; Chakrabarti, Kristi R ; Alvarez, James V ; Ruth, Jason R ; Chodosh, Lewis A

Breast cancer mortality is principally due to tumor recurrence, however the molecular mechanisms underlying this process are poorly understood. We now demonstrate that the SOCS protein SPSB1 is spontaneously up-regulated during mammary tumor recurrence and is both necessary and sufficient to promote tumor recurrence in genetically engineered mouse models. The recurrence-promoting effects of SPSB1 result from its ability to protect cells from apoptosis induced by HER2/neu pathway inhibition or [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels des facteurs induits par l'hypoxie intratumorale favorisent les processus invasif et métastatique d'un cancer du sein triplement négatif

Hypoxia-inducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment

Chaturvedi, Pallavi ; Gilkes, Daniele M. ; Takano, Naoharu ; Semenza, Gregg L.

Intratumoral hypoxia induces the recruitment of stromal cells, such as macrophages and mesenchymal stem cells (MSCs), which stimulate invasion and metastasis by breast cancer cells (BCCs). Production of macrophage colony-stimulating factor 1 (CSF1) by BCCs is required for macrophage recruitment, but the mechanisms underlying CSF1 expression have not been delineated. Triple-negative breast cancers have increased expression of genes regulated by hypoxia-inducible factors (HIFs). In this study, we [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels la protéine Gremlin1 est sécrétée par les cellules souches cancéreuses pour favoriser la prolifération d'un glioblastome

Glioma cancer stem cells secrete Gremlin1 to promote their maintenance within the tumor hierarchy

Yan, Kenneth ; Wu, Qiulian ; Yan, Diana H. ; Lee, Christine H. ; Rahim, Nasiha ; Tritschler, Isabel ; DeVecchio, Jennifer ; Kalady, Matthew F. ; Hjelmeland, Anita B. ; Rich, Jeremy N.

Glioblastomas are the most prevalent and lethal primary brain tumor and are comprised of hierarchies with self-renewing cancer stem cells (CSCs) at the apex. Like neural stem cells (NSCs), CSCs reside in functional niches that provide essential cues to maintain the cellular hierarchy. Bone morphogenetic proteins (BMPs) instruct NSCs to adopt an astrocyte fate and are proposed as anti-CSC therapies to induce differentiation, but, paradoxically, tumors express high levels of BMPs. Here we [...]

Cet article passe en revue les méthodes d'analyse intégrée de données génomiques, métabolomiques et cliniques

Principles and methods of integrative genomic analyses in cancer

Kristensen, Vessela N. ; Lingjaerde, Ole Christian ; Russnes, Hege G. ; Vollan, Hans Kristian M. ; Frigessi, Arnoldo ; Borresen-Dale, Anne-Lise

Combined analyses of molecular data, such as DNA copy-number alteration, mRNA and protein expression, point to biological functions and molecular pathways being deregulated in multiple cancers. Genomic, metabolomic and clinical data from various solid cancers and model systems are emerging and can be used to identify novel patient subgroups for tailored therapy and monitoring. The integrative genomics methodologies that are used to interpret these data require expertise in different [...]

Cet article passe en revue les travaux récents sur le rôle de la flore microbienne intestinale dans le développement d'un cancer du côlon

The Multifaceted Role of the Intestinal Microbiota in Colon Cancer

Irrazábal, Thergiory ; Belcheva, Antoaneta ; Girardin, Stephen E ; Martin, Alberto ; Philpott, Dana J

In recent years, our understanding of the mechanisms underlying colorectal carcinogenesis has vastly expanded. Underlying inflammation within the intestine, diet, and most recently, the gut microbiota, have been demonstrated to influence the development of colorectal cancer. However, since cancer is ultimately a genetic disease, these factors are thought to create genotoxic stress within the intestinal environment to promote genetic and epigenetic alterations leading to cancer. In this review, [...]