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CRC subtypes

Wei Wang, Raju Kandimalla, Hao Huang, Lina Zhu, Ying Li, Feng Gao, Ajay Goel, Xin Wang
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Similar to many other malignancies, CRC is a heterogeneous disease, making it a clinical challenge for optimization of treatment modalities in reducing the morbidity and mortality associated with this disease. A more precise understanding of the biological properties that distinguish patients with colorectal tumors, especially in terms of their clinical features, is a key requirement towards a more robust, targeted-drug design, and implementation of individualized therapies...
May 15, 2018: Seminars in Cancer Biology
Lu Shi, Xiang Li, Zhiqiang Wu, Xiaolei Li, Jing Nie, Mingzhou Guo, Qian Mei, Weidong Han
Microsatellite instability (MSI) defines a subtype of colorectal cancer (CRC) with typical clinicopathologic characteristics. CRCs with MSI (MSI CRCs) frequently acquire accelerated carcinogenesis and 5-FU resistance, and the exact underlying mechanism remains incompletely understood. Our previous study has identified the microRNA (miRNA) expression profile in MSI CRCs. In this study, three miRNAs (miR-181a, miR-135a and miR-302c) were validated by qRT-PCR to be dramatically decreased in 67 CRC samples. Proliferation and apoptosis assays demonstrated that miR-181a/135a/302c function as tumor suppressors via repressing PLAG1/IGF2 signaling...
April 13, 2018: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Jessica A Hemminger, Rachel Pearlman, Sigurdis Haraldsdottir, Deborah Knight, Jon Gunnlaugur Jonasson, Colin C Pritchard, Heather Hampel, Wendy L Frankel
Lynch syndrome (LS) is the most common form of hereditary colon cancer (CRC). Germline mutations in the mismatch repair (MMR) genes MLH1, MSH2 (EPCAM), MSH6, and PMS2, followed by a second hit to the remaining allele leads to cancer development. Universal tumor screening for LS is routinely performed on CRC, and screening has identified patients with unexplained MMR deficiency that lack MLH1 methylation and a germline mutation. Tumor sequencing has since identified double somatic (DS) mutations in the MMR gene corresponding with the absent protein in 69% of these patients...
April 30, 2018: Human Pathology
Akira Okita, Shin Takahashi, Kota Ouchi, Masahiro Inoue, Mika Watanabe, Mareyuki Endo, Hiroshi Honda, Yasuhide Yamada, Chikashi Ishioka
The consensus molecular subtypes (CMS) classification is one of the most robust colorectal cancer (CRC) classifications based on comprehensive gene expression profiles. This study aimed to clarify whether the CMS is a predictive factor for therapeutic effects of standard chemotherapies for metastatic CRC (mCRC). We retrospectively enrolled 193 patients with mCRCs, and using comprehensive gene expression data, classified them into 4 subtypes: CMS1-CMS4. The associations between the subtypes and treatment outcomes were analyzed...
April 10, 2018: Oncotarget
Jonathan M Loree, Ann M Bailey, Amber M Johnson, Yao Yu, Wenhui Wu, Christopher A Bristow, Jennifer S Davis, Kenna R Shaw, Russell Broaddus, Kimberly C Banks, Richard B Lanman, Funda Meric-Bernstam, Michael J Overman, Scott Kopetz, Kanwal Raghav
Background: Despite growing therapeutic relevance of ERBB2 amplifications in colorectal cancer (CRC), little is known about ERBB2/ERBB3 mutations. We aimed to characterize these subsets of CRC. Methods: We performed a retrospective analysis of 419 CRC patients from MD Anderson (MDACC) and 619 patients from the Nurses' Health Study (NHS)/Health Professionals Follow-Up Study (HPFS) with tissue sequencing, clinicopathologic, mutational, and consensus molecular subtype (CMS) profiles of ERBB2/ERBB3 mutant patients...
April 27, 2018: Journal of the National Cancer Institute
Lei Chen, Xiaoyong Pan, XiaoHua Hu, Yu-Hang Zhang, ShaoPeng Wang, Tao Huang, Yu-Dong Cai
Colorectal cancer is the third most common cancer in males and second in females. This disease can be caused by genetic and acquired/environmental factors. Microsatellite instability (MSI) is one of the major mechanisms in colorectal cancer. This mechanism is a specific condition of genetic hyper mutability that results from incompetent DNA mismatch repair. MSI has been applied to classify different colorectal cancer subtypes. However, the effects of MSI status on gene expression are largely unknown. In this study, we integrated the gene expression profile and MSI status of all CRC samples from the TCGA database, and then categorized the CRC samples into three subgroups, namely, MSI-stable, MSI-low, and MSI-high, according to the MSI status...
April 26, 2018: International Journal of Cancer. Journal International du Cancer
Robin Myte, Björn Gylling, Jenny Häggström, Jörn Schneede, Anna Löfgren-Burström, Jeroen R Huyghe, Göran Hallmans, Klaus Meyer, Ingegerd Johansson, Per Magne Ueland, Richard Palmqvist, Bethany Van Guelpen
Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes...
2018: PloS One
Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec, Miao Yang, Jia Q Ng, Nobumi Suzuki, Mari Ichinose, Josephine A Wright, Hiroki Kobayashi, Tracey L Putoczki, Yoku Hayakawa, Simon J Leedham, Helen E Abud, Ömer H Yilmaz, Julie Marker, Sonja Klebe, Pratyaksha Wirapati, Siddhartha Mukherjee, Sabine Tejpar, Barbara A Leggett, Vicki L J Whitehall, Daniel L Worthley, Susan L Woods
OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF , and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein...
April 17, 2018: Gut
Laura Barrubés, Nancy Babio, Guillermo Mena-Sánchez, Estefania Toledo, Judith B Ramírez-Sabio, Ramón Estruch, Emilio Ros, Montserrat Fitó, Fernando Arós, Miquel Fiol, José Manuel Santos-Lozano, Lluís Serra-Majem, Xavier Pintó, Miguel Ángel Martínez-González, José Vicente Sorlí, Josep Basora, Jordi Salas-Salvadó
Prospective studies have reported an inverse association between the consumption of total dairy products and milk and the risk of colorectal cancer (CRC). Nonetheless, there is little and inconsistent evidence regarding subtypes of dairy product and CRC risk. We assessed the associations between the consumption of total dairy products, their different subtypes and CRC risk in older Mediterranean individuals at high cardiovascular risk. We analyzed data from 7,216 men and women (55-80 years) without CRC at baseline from the PREvención con DIeta MEDiterránea study...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
Wang Gang, Jun-Jie Wang, Rui Guan, Sun Yan, Feng Shi, Jia-Yan Zhang, Zi-Meng Li, Jing Gao, Xing-Li Fu
Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T-cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy...
April 15, 2018: Cancer Medicine
Sanne Ten Hoorn, Anne Trinh, Joan de Jong, Lianne Koens, Louis Vermeulen
Colorectal cancer (CRC) is a heterogeneous disease, which can be categorized into distinct consensus molecular subtypes (CMSs). These subtypes differ in both clinical as well as biological properties. The gold-standard classification strategy relies on genome-wide expression data, which hampers widespread implementation. Here we describe an immunohistochemical (IHC) Mini Classifier, a practical tool that, in combination with microsatellite instability testing, delivers objective and accurate scoring to classify CRC patients into the main molecular disease subtypes...
2018: Methods in Molecular Biology
Jennifer K Mooi, Ian Y Luk, John M Mariadason
Colorectal cancer (CRC) is a genetically diverse disease necessitating the need for well-characterized and reproducible models to enable its accurate investigation. Recent genomic analyses have confirmed that CRC cell lines accurately retain the key genetic alterations and represent the major molecular subtypes of primary CRC, underscoring their value as powerful preclinical models. In this chapter we detail the important issues to consider when using CRC cell lines, the techniques used for their appropriate molecular classification, and the methods by which they are cultured in vitro and as subcutaneous xenografts in immune-compromised mice...
2018: Methods in Molecular Biology
Steven A Signs, Robert C Fisher, Uyen Tran, Susmita Chakrabarti, Samaneh K Sarvestani, Shao Xiang, David Liska, Veronique Roche, Wei Lai, Haley R Gittleman, Oliver Wessely, Emina H Huang
Inflammatory bowel disease (IBD) affects one million people in the US. Ulcerative colitis (UC) is a subtype of IBD that can lead to colitis-associated cancer (CAC). In UC, the rate of CAC is 3-5-fold greater than the rate of sporadic colorectal cancer (CRC). The pathogenesis of UC and CAC are due to aberrant interactions between host immune system and microenvironment, but precise mechanisms are still unknown. In colitis and CAC, microenvironmental fibroblasts exhibit an activated, inflammatory phenotype that contributes to tumorigenesis accompanied by excessive secretion of the chemokine CXCL8...
February 27, 2018: Oncotarget
Hironori Aoki, Eiichiro Yamamoto, Hiro-O Yamano, Tamotsu Sugai, Tomoaki Kimura, Yoshihito Tanaka, Hiro-O Matsushita, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Michiko Nakaoka, Yuko Yoshida, Taku Harada, Gota Sudo, Makoto Eizuka, Akira Yorozu, Hiroshi Kitajima, Takeshi Niinuma, Masahiro Kai, Masanori Nojima, Hiromu Suzuki, Hiroshi Nakase
BACKGROUND: Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. AIMS: We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. METHODS: A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L)...
March 15, 2018: Digestive Diseases and Sciences
J Smeby, A Sveen, M A Merok, S A Danielsen, I A Eilertsen, M G Guren, R Dienstmann, A Nesbakken, R A Lothe
BACKGROUND: The prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer (CRC) varies with microsatellite instability (MSI) status. The gene expression-based consensus molecular subtypes (CMS) of CRC define molecularly and clinically distinct subgroups, and represent a novel stratification framework in biomarker analysis. We investigated the prognostic value of these mutations within the CMS groups. PATIENTS AND METHODS: Totally 1197 primary tumors from a Norwegian series of CRC stage I-IV were analyzed for MSI and mutation status in hotspots in KRAS (codons 12, 13 and 61) and BRAF (codon 600)...
March 5, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Catherine S Grasso, Marios Giannakis, Daniel K Wells, Tsuyoshi Hamada, Xinmeng Jasmine Mu, Michael Quist, Jonathan A Nowak, Reiko Nishihara, Zhi Rong Qian, Kentaro Inamura, Teppei Morikawa, Katsuhiko Nosho, Gabriel Abril-Rodriguez, Charles Connolly, Helena Escuin-Ordinas, Milan S Geybels, William M Grady, Li Hsu, Siwen Hu-Lieskovan, Jeroen R Huyghe, Yeon Joo Kim, Paige Krystofinski, Mark D M Leiserson, Dennis J Montoya, Brian B Nadel, Matteo Pellegrini, Colin C Pritchard, Cristina Puig-Saus, Elleanor H Quist, Ben J Raphael, Stephen J Salipante, Daniel Sanghoon Shin, Eve Shinbrot, Brian Shirts, Sachet Shukla, Janet L Stanford, Wei Sun, Jennifer Tsoi, Alexander Upfill-Brown, David A Wheeler, Catherine J Wu, Ming Yu, Syed H Zaidi, Jesse M Zaretsky, Stacey B Gabriel, Eric S Lander, Levi A Garraway, Thomas J Hudson, Charles S Fuchs, Antoni Ribas, Shuji Ogino, Ulrike Peters
To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity...
March 6, 2018: Cancer Discovery
Micaela Freitas, Fábio Ferreira, Sónia Carvalho, Fernanda Silva, Paula Lopes, Luís Antunes, Sofia Salta, Francisca Diniz, Lúcio Lara Santos, José Flávio Videira, Rui Henrique, Carmen Jerónimo
BACKGROUND: Colorectal cancer (CRC) is one of the most incident cancers, associated with significant morbidity and mortality, and usually classified into three main molecular pathways: chromosomal instability, microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Currently, available screening methods are either costly or of limited specificity, impairing global implementation. More cost-effective strategies, including DNA methylation-based tests, might prove advantageous...
February 27, 2018: Journal of Translational Medicine
Gabriele Romano, Sharmeen Chagani, Lawrence N Kwong
The study and comprehension of the molecular mechanisms underlying cancer biology strongly rely on mouse modeling. An ideal mouse model should have molecular, histopathological, and etiological characteristics as close as possible to those of the corresponding human tumors. Among solid tumors, colorectal cancer (CRC) is one of the malignancies that best suits reproduction in an animal model: it evolves through a progressive set of molecular events and is generally associated with a precise histopathology and a neat cataloging of stages and grades...
February 21, 2018: Oncogene
Hossein Molavi Vardanjani, AliAkbar Haghdoost, Kamran Bagheri-Lankarani, Maryam Hadipour
Background: Population aging and more prevalent westernized lifestyle would be expected to result in a markedly rising burden of colorectal cancer (CRC) in the future years. The aim of this study is to estimate the limited-time prevalence of CRC in Iran between 2015 and 2020. Materials and Methods: Aggregated CRC incidence data were extracted from the Iranian national cancer registry (IR.NCR) reports for 2003-2009 and from GLOBOCAN-2012 database for 2012. Incidence trends were analyzed by age groups, genders, histopathologic, and topographic subtypes to estimate annual percentage changes...
2018: Advanced Biomedical Research
P R Carr, E Alwers, S Bienert, J Weberpals, M Kloor, H Brenner, M Hoffmeister
Introduction: The association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status. Methods: PubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC...
April 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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