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https://www.readbyqxmd.com/read/28340142/multigene-signature-for-predicting-prognosis-of-patients-with-1p19q-co-deletion-diffuse-glioma
#1
Xin Hu, Emmanuel Martinez-Ledesma, Siyuan Zheng, Hoon Kim, Floris Barthel, Tao Jiang, Kenneth R Hess, Roel G W Verhaak
Background.: Co-deletion of 1p and 19q marks a diffuse glioma subtype associated with relatively favorable overall survival; however, heterogeneous clinical outcomes are observed within this category. Methods.: We assembled gene expression profiles and sample annotation of 374 glioma patients carrying the 1p/19q co-deletion. We predicted 1p/19q status using gene expression when annotation was missing. A first cohort was randomly split into training (n = 170) and a validation dataset (n = 163)...
March 8, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339723/leveraging-molecular-datasets-for-biomarker-based-clinical-trial-design-in-glioblastoma
#2
Shyam K Tanguturi, Lorenzo Trippa, Shakti H Ramkissoon, Kristine Pelton, David Knoff, David Sandak, Neal I Lindeman, Azra H Ligon, Rameen Beroukhim, Giovanni Parmigiani, Patrick Y Wen, Keith L Ligon, Brian M Alexander
Background.: Biomarkers can improve clinical trial efficiency, but designing and interpreting biomarker-driven trials require knowledge of relationships among biomarkers, clinical covariates, and endpoints. We investigated these relationships across genomic subgroups of glioblastoma (GBM) within our institution (DF/BWCC), validated results in The Cancer Genome Atlas (TCGA), and demonstrated potential impacts on clinical trial design and interpretation. Methods.: We identified genotyped patients at DF/BWCC, and clinical associations across 4 common GBM genomic biomarker groups were compared along with overall survival (OS), progression-free survival (PFS), and survival post-progression (SPP)...
February 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339086/identification-of-novel-mutations-in-endometrial-cancer-patients-by-whole-exome-sequencing
#3
Ya-Sian Chang, Hsien-Da Huang, Kun-Tu Yeh, Jan-Gowth Chang
The aim of the present study was to identify genomic alterations in Taiwanese endometrial cancer patients. This information is vitally important in Taiwan, where endometrial cancer is the second most common gynecological cancer. We performed whole-exome sequencing on DNA from 14 tumor tissue samples from Taiwanese endometrial cancer patients. We used the Genome Analysis Tool kit software package for data analysis, and the dbSNP, Catalogue of Somatic Mutations in Cancer (COSMIC) and The Cancer Genome Atlas (TCGA) databases for comparisons...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338654/tfeb-vegfa-6p21-1-co-amplified-renal-cell-carcinoma-a-distinct-entity-with-potential-implications-for-clinical-management
#4
Sounak Gupta, Sarah H Johnson, George Vasmatzis, Binu Porath, Jeannette G Rustin, Priya Rao, Brian A Costello, Bradley C Leibovich, R Houston Thompson, John C Cheville, William R Sukov
A subset of renal cell carcinomas shows TFEB overexpression secondary to MALAT1-TFEB gene fusion. As alternate mechanisms of TFEB overexpression are likely to have the same effect, we sought to determine the frequency of amplification of TFEB and the adjacent VEGFA gene at 6p21.1. As patients with metastatic renal cell carcinomas are managed with anti-VEGF therapies, we retrospectively assessed therapeutic response in patients with amplified tumors. Amplification status was analyzed for 875 renal cell carcinomas from our institution, a consultative case and 794 cases from The Cancer Genome Atlas...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28338236/hsa-mir-3199-2-and-hsa-mir-1293-as-novel-prognostic-biomarkers-of-papillary-renal-cell-carcinoma-by-cox-ratio-risk-regression-model-screening
#5
Wen Luo, Lei Wang, Mao-Hua Luo, Yu-Zhu Huang, Hua Yang, Yu Zhou, Hong-Tao Jia, Xiu-Xin Wang
Papillary renal cell carcinoma(PRCC) is the second most common and aggressive renal cell carcinoma. Identification of novel microRNA biomarkers could be beneficial for the diagnosis and prognosis of PRCCpatients.We aimed to screen differentially expressed miRNAs that can act as prognostic factors and to predict the survival of PRCC patients. High-throughput data of miRNAs of 274 PRCC samples were downloaded from TCGA(The Cancer Genome Atlas) dataset and interested miRNAs were identified. Hierarchical clustering and principal component analysis (PCA) were performed on these miRNAs...
March 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28334343/pathwaymapper-a-collaborative-visual-web-editor-for-cancer-pathways-and-genomic-data
#6
Istemi Bahceci, Ugur Dogrusoz, Konnor C La, Özgün Babur, Jianjiong Gao, Nikolaus Schultz
Motivation: While existing network visualization tools enable the exploration of cancer genomics data, most biologists prefer simplified, curated pathway diagrams, such as those featured in many manuscripts from The Cancer Genome Atlas (TCGA). These pathway diagrams typically summarize how a pathway is altered in individual cancer types, including alteration frequencies for each gene. Results: To address this need, we developed the web-based tool PathwayMapper, which runs in most common web browsers...
March 16, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28334118/individualized-analysis-of-differentially-expressed-mirnas-with-application-to-the-identification-of-mirnas-deregulated-commonly-in-lung-cancer-tissues
#7
Haidan Yan, Hao Cai, Qingzhou Guan, Jun He, Juan Zhang, You Guo, Haiyan Huang, Xiangyu Li, Yawei Li, Yunyan Gu, Lishuang Qi, Zheng Guo
Identifying differentially expressed microRNAs (DE miRNAs) between cancer samples and normal controls is a common way to investigate carcinogenesis mechanisms. However, for a DE miRNA detected at the population-level, we do not know whether it is DE in a particular cancer sample. Here, based on the finding that the within-sample relative expression orderings of miRNA pairs are highly stable in a particular type of normal tissues but widely disrupted in the corresponding cancer tissues, we proposed a method, called RankMiRNA, to identify DE miRNAs in each cancer tissue compared with its own normal state...
February 23, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28325946/epigenetically-regulated-fibronectin-leucine-rich-transmembrane-protein-2-flrt2-shows-tumor-suppressor-activity-in-breast-cancer-cells
#8
Hansol Bae, Byungtak Kim, Hyunkyung Lee, Seungyeon Lee, Han-Sung Kang, Sun Jung Kim
To identify dysregulated genes by abnormal methylation and expression in breast cancer, we genome-wide analyzed methylation and expression microarray data from the Gene Expression Omnibus and the Cancer Genome Atlas database. One of the genes screened in silico, FLRT2, showed hypermethylation and downregulation in the cancer dataset and the association was verified both in cultured cell lines and cancer patients' tissue. To investigate the role of FLRT2 in breast cancer, its expression was knocked down and upregulated in mammary cell lines, and the effect was examined through three levels of approach: pathway analysis; cell activities such as proliferation, colony formation, migration, and adhesion; target gene expression...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324890/regulation-of-itga3-by-the-dual-stranded-microrna-199-family-as-a-potential-prognostic-marker-in-bladder-cancer
#9
Takashi Sakaguchi, Hirofumi Yoshino, Masaya Yonemori, Kazutaka Miyamoto, Satoshi Sugita, Ryosuke Matsushita, Toshihiko Itesako, Shuichi Tatarano, Masayuki Nakagawa, Hideki Enokida
BACKGROUND: Based on the microRNA (miRNA) signature of bladder cancer (BC) by deep sequencing, we recently found that several double-stranded mature miRNAs derived from the same pre-miRNAs were sufficiently expressed and acted as tumour suppressors by regulating common target genes in BC. Our deep-sequencing signature of BC showed that all miR-199 family members (miR-199a-3p/-5p and miR-199b-3p/-5p) were also downregulated. We hypothesised that these miRNAs may function as tumour suppressors by regulating common target genes...
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28322996/assessing-the-mirna-sponge-potential-of-runx1t1-in-t-8-21-acute-myeloid-leukemia
#10
Alexander Junge, Roza Zandi, Jakob Hull Havgaard, Jan Gorodkin, Jack Bernard Cowland
t(8;21) acute myeloid leukemia (AML) is characterized by a translocation between chromosomes 8 and 21 and formation of a distinctive RUNX1-RUNX1T1 fusion transcript. This translocation places RUNX1T1 under control of the RUNX1 promoter leading to a pronounced upregulation of RUNX1T1 transcripts in t(8;21) AML, compared to normal hematopoietic cells. We investigated the role of highly-upregulated RUNX1T1 under the hypothesis that it acts as competing endogenous RNA (ceRNA) titrating microRNAs (miRNAs) away from their target transcripts and thus contributes to AML formation...
March 16, 2017: Gene
https://www.readbyqxmd.com/read/28322348/several-micrornas-could-predict-survival-in-patients-with-hepatitis-b-related-liver-cancer
#11
Ye Zhen, Zhao Xinghui, Wu Chao, Zhao Yi, Chen Jinwen, Gao Ruifang, Zhang Chao, Zhao Min, Guo Chunlei, Fang Yan, Du Lingfang, Shen Long, Shen Wenzhi, Luo Xiaohe, Xiang Rong
MicroRNAs as biomarkers play an important role in the tumorigenesis process, including hepatocellular carcinomas (HCCs). In this paper, we used The Cancer Genome Atlas (TCGA) database to mine hepatitis B-related liver cancer microRNAs that could predict survival in patients with hepatitis B-related liver cancer. There were 93 cases of HBV-HCC and 49 cases of adjacent normal controls included in the study. Kaplan-Meier survival analysis of a liver cancer group versus a normal control group of differentially expressed genes identified eight genes with statistical significance...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321693/age-at-diagnosis-obesity-smoking-and-molecular-subtypes-in-muscle-invasive-bladder-cancer
#12
Xuezheng Sun, Katherine A Hoadley, William Y Kim, Helena Furberg, Andrew F Olshan, Melissa A Troester
BACKGROUND: Heterogeneity of muscle-invasive bladder cancer (MIBC) has been characterized using whole-genome mRNA expression data, showing distinct molecular and clinicopathological characteristics by subtypes. However, associations between risk factors and molecular subtypes have not been reported. METHODS: Four previously published schemes were used to categorize molecular subtypes in 372 MIBC patients from the Cancer Genome Atlas (TCGA). Data on gene expression (RNA-seq), demographic, and clinicopathological characteristics were retrieved through TCGA data portal...
March 20, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28319171/a-reported-20-gene-expression-signature-to-predict-lymph-node-positive-disease-at-radical-cystectomy-for-muscle-invasive-bladder-cancer-is-clinically-not-applicable
#13
Kim E M van Kessel, Harmen J G van de Werken, Irene Lurkin, Angelique C J Ziel-van der Made, Ellen C Zwarthoff, Joost L Boormans
BACKGROUND: Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that predicted lymph node-positive disease at radical cystectomy in clinically node-negative MIBC patients, which would be a justification for upfront chemotherapy...
2017: PloS One
https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#14
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28317894/swim-a-computational-tool-to-unveiling-crucial-nodes-in-complex-biological-networks
#15
Paola Paci, Teresa Colombo, Giulia Fiscon, Aymone Gurtner, Giulio Pavesi, Lorenzo Farina
SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called "fight-club hubs", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called "switch genes", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28316892/from-big-data-to-diagnosis-and-prognosis-gene-expression-signatures-in-liver-hepatocellular-carcinoma
#16
Hong Yang, Xin Zhang, Xiao-Yong Cai, Dong-Yue Wen, Zhi-Hua Ye, Liang Liang, Lu Zhang, Han-Lin Wang, Gang Chen, Zhen-Bo Feng
BACKGROUND: Liver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in. METHODS: Big data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes...
2017: PeerJ
https://www.readbyqxmd.com/read/28314692/identification-of-an-atypical-etiological-head-and-neck-squamous-carcinoma-subtype-featuring-the-cpg-island-methylator-phenotype
#17
K Brennan, J L Koenig, A J Gentles, J B Sunwoo, O Gevaert
Head and neck squamous cell carcinoma (HNSCC) is broadly classified into HNSCC associated with human papilloma virus (HPV) infection, and HPV negative HNSCC, which is typically smoking-related. A subset of HPV negative HNSCCs occur in patients without smoking history, however, and these etiologically 'atypical' HNSCCs disproportionately occur in the oral cavity, and in female patients, suggesting a distinct etiology. To investigate the determinants of clinical and molecular heterogeneity, we performed unsupervised clustering to classify 528 HNSCC patients from The Cancer Genome Atlas (TCGA) into putative intrinsic subtypes based on their profiles of epigenetically (DNA methylation) deregulated genes...
March 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28314268/clinical-significance-of-fancd2-gene-expression-and-its-association-with-tumor-progression-in-hepatocellular-carcinoma
#18
Hisateru Komatsu, Takaaki Masuda, Tomohiro Iguchi, Sho Nambara, Kuniaki Sato, Quingjang Hu, Hidenari Hirata, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori
BACKGROUND/AIM: Fanconi anemia complementation group D2 (FANCD2) gene is vitally involved in DNA damage responses. We investigated the clinical significance of FANCD2 expression in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: FANCD2 mRNA expression of resected HCC tissues was assessed in two HCC cohorts; Our cases (n=111), and The Cancer Genome Atlas (TCGA; n=371). Gene set enrichment analysis (GSEA) was conducted using the TCGA dataset. Proliferation and invasion assays were performed using siRNAs, and the effect of inhibition of the mechanistic target of rapamycin (mTOR) pathway was evaluated...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28304380/comprehensive-analysis-of-the-cancer-genome-atlas-reveals-a-unique-gene-and-non-coding-rna-signature-of-fibrolamellar-carcinoma
#19
Timothy A Dinh, Eva C M Vitucci, Eliane Wauthier, Rondell P Graham, Wendy A Pitman, Tsunekazu Oikawa, Mengjie Chen, Grace O Silva, Kevin G Greene, Michael S Torbenson, Lola M Reid, Praveen Sethupathy
Fibrolamellar carcinoma (FLC) is a unique liver cancer primarily affecting young adults and characterized by a fusion event between DNAJB1 and PRKACA. By analyzing RNA-sequencing data from The Cancer Genome Atlas (TCGA) for >9,100 tumors across ~30 cancer types, we show that the DNAJB1-PRKACA fusion is specific to FLCs. We demonstrate that FLC tumors (n = 6) exhibit distinct messenger RNA (mRNA) and long intergenic non-coding RNA (lincRNA) profiles compared to hepatocellular carcinoma (n = 263) and cholangiocarcinoma (n = 36), the two most common liver cancers...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297679/integrative-genomic-analysis-of-cholangiocarcinoma-identifies-distinct-idh-mutant-molecular-profiles
#20
Farshad Farshidfar, Siyuan Zheng, Marie-Claude Gingras, Yulia Newton, Juliann Shih, A Gordon Robertson, Toshinori Hinoue, Katherine A Hoadley, Ewan A Gibb, Jason Roszik, Kyle R Covington, Chia-Chin Wu, Eve Shinbrot, Nicolas Stransky, Apurva Hegde, Ju Dong Yang, Ed Reznik, Sara Sadeghi, Chandra Sekhar Pedamallu, Akinyemi I Ojesina, Julian M Hess, J Todd Auman, Suhn K Rhie, Reanne Bowlby, Mitesh J Borad, Andrew X Zhu, Josh M Stuart, Chris Sander, Rehan Akbani, Andrew D Cherniack, Vikram Deshpande, Taofic Mounajjed, Wai Chin Foo, Michael S Torbenson, David E Kleiner, Peter W Laird, David A Wheeler, Autumn J McRee, Oliver F Bathe, Jesper B Andersen, Nabeel Bardeesy, Lewis R Roberts, Lawrence N Kwong
Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number...
March 14, 2017: Cell Reports
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