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The cancer genome atlas

Yosuke Hirotsu, Yuichiro Kojima, Kenichiro Okimoto, Kenji Amemiya, Hitoshi Mochizuki, Masao Omata
BACKGROUND: Sequencing data from The Cancer Genome Atlas (TGCA), the International Cancer Genome Consortium and other research institutes have revealed the presence of genetic alterations in several tumor types, including gastric cancer. These data have been combined into a catalog of significantly mutated genes for each cancer type. However, it is unclear to what extent significantly mutated genes need to be examined for detecting genetic alterations in gastric cancer patients. Here, we constructed two custom-made sequencing panels of different scales, the Selective hotspot Panel and the Comprehensive Panel, to analyze genetic alterations in 21 resected specimens endoscopically obtained from 20 gastric cancer patients, and we assessed how many mutations were detectable using these different panels...
October 26, 2016: BMC Genomics
Ahmad Chaddad, Christian Desrosiers, Lama Hassan, Camel Tanougast
OBJECTIVE: Predicting the survival outcome of glioblastoma multiforme (GBM) patients is of key importance to clinicians for selecting the optimal course of treatment. The goal of this study is to evaluate the usefulness of geometric shape features, extracted from MRI images, as a potential non-invasive way to characterize GBM tumors and predict the overall survival times of GBM patients. METHODS: The data of 40 GBM patients were obtained from the Cancer Genome Atlas and Cancer Imaging Archive...
October 26, 2016: British Journal of Radiology
Marla Johnson, Elizabeth Purdom
Sequencing of messenger RNA (mRNA) can provide estimates of the levels of individual isoforms within the cell. It remains to adapt many standard statistical methods commonly used for analyzing gene expression levels to take advantage of this additional information. One novel question is whether we can find clusters of samples that are distinguished not by their gene expression but by their isoform usage. We propose a novel approach for clustering mRNA-Seq data that identifies such clusters. We show via simulation that our methods are more sensitive to finding clusters based on isoform usage than standard clustering techniques...
October 25, 2016: Biostatistics
Anna M Dahlin, Carl Wibom, Soma Ghasimi, Thomas Brännström, Ulrika Andersson, Beatrice Melin
Genome-wide association studies and candidate gene studies have identified several genetic variants that increase glioma risk. The majority of these variants are non-coding and the mechanisms behind the increased risk in carriers are not known. In this study, we hypothesize that some of the established glioma risk variants induce aberrant DNA methylation in the developing tumor, either locally (gene-specific) or globally (genome-wide). In a pilot data set including 77 glioma patients, we used Illumina beadchip technology to analyze genetic variants in blood and DNA methylation in matched tumor samples...
2016: PloS One
Desheng Lv, Run Sun, Qian Yu, Xuefei Zhang
Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor survival. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and cancer progression; hence, lncRNAs are also involved in the development and progression of ESCC. In this study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to investigate expression of lncRNA, maternally expressed gene 3 (MEG3) in ESCC. Ectopic expression of MEG3 was performed in ESCC cell lines. Proliferation and apoptosis of ESCC cell lines were analyzed after ectopic expression of MEG3...
October 24, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
F Chen, Y Zhang, E Parra, J Rodriguez, C Behrens, R Akbani, Y Lu, J M Kurie, D L Gibbons, G B Mills, I I Wistuba, C J Creighton
Non-small-cell lung cancer (NSCLC) demonstrates remarkable molecular diversity. With the completion of The Cancer Genome Atlas (TCGA), there is opportunity for systematic analyses of the entire TCGA NSCLC cohort, including comparisons and contrasts between different disease subsets. On the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy, and RNA and protein expression), 1023 NSCLC cases-519 from TCGA adenocarcinoma (AD) project and 504 from TCGA squamous cell carcinoma (SQCC) project-were classified using a 'cluster-of-clusters' analytic approach...
October 24, 2016: Oncogene
Shizhong Ke, Shuzhen Chen, Zihui Dong, Christopher S Hong, Qi Zhang, Liang Tang, Pinghua Yang, Jian Zhai, Hexin Yan, Feng Shen, Zhengping Zhuang, Wen Wen, Hongyang Wang
: Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma (HCC). Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. Here we demonstrated an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas (TCGA). In the subset of HCC patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting impairment of respiratory metabolism, which sequentially led to depletion of α-ketoglutarate, stabilization of hypoxia inducible factor-α and expression of target genes such as EPO...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Feixiong Cheng, Junfei Zhao, Ariella B Hanker, Monica Red Brewer, Carlos L Arteaga, Zhongming Zhao
PURPOSE: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in human breast cancer. Furthermore, PIK3CA mutations are commonly associated with resistance to anti-epidermal growth factor receptor 2 (HER2) or anti-estrogen receptor (ER) agents in HER2 or ER positive (HER2(+)/ER(+)) breast cancer. Hence, deciphering the underlying mechanisms of PIK3CA mutations in HER2(+)/ER(+) breast cancer would provide novel insights into elucidating resistance to anti-HER2/ER therapies...
October 22, 2016: Breast Cancer Research and Treatment
Tatsuo Kido, Yun-Fai Chris Lau
Testis specific protein Y-encoded (TSPY) is a Y-located proto-oncogene predominantly expressed in normal male germ cells and various types of germ cell tumor. Significantly, TSPY is frequently expressed in somatic cancers including liver cancer but not in adjacent normal tissues, suggesting that ectopic TSPY expression could be associated with oncogenesis in non-germ cell cancers. Various studies demonstrated that TSPY expression promotes growth and proliferation in cancer cells; however, its relationship to other oncogenic events in TSPY-positive cancers remains unknown...
September 17, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Barbara Wolf, Georg Goebel, Hubert Hackl, Heidi Fiegl
BACKGROUND: The transcription factor nuclear factor erythroid 2-related factor 2 (NFE2L2; previously known as NRF2) is a crucial regulator of the intracellular antioxidant response. It controls the expression of genes involved in the detoxification and elimination of reactive oxidants and electrophilic agents. The role of NFE2L2 in cancer is subject of controversial discussion, as it has been reported to have both pro-and anti-tumourigenic functions. To shed some light on this paradox, we analysed the NFE2L2 mRNA expression levels in breast cancer and its association with clinicopathological features and survival...
October 22, 2016: BMC Cancer
Hisateru Komatsu, Tomohiro Iguchi, Takaaki Masuda, Hidenari Hirata, Masami Ueda, Shinya Kidogami, Yushi Ogawa, Kuniaki Sato, Qingjiang Hu, Sho Nambara, Tomoko Saito, Shotaro Sakimura, Ryutaro Uchi, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori
BACKGROUND: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). METHODS: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520...
October 21, 2016: Annals of Surgical Oncology
Yongsheng Bai, Lizhong Ding, Steve Baker, Jenny M Bai, Ethan Rath, Feng Jiang, Jianghong Wu, Hui Jiang, Gary Stuart
BACKGROUND: MicroRNAs (miRNA) are short nucleotides that interact with their target genes through 3' untranslated regions (UTRs). The Cancer Genome Atlas (TCGA) harbors an increasing amount of cancer genome data for both tumor and normal samples. However, there are few visualization tools focusing on concurrently displaying important relationships and attributes between miRNAs and mRNAs of both cancer tumor and normal samples. Moreover, a deep investigation of miRNA-mRNA target and biological relationships across multiple cancer types by integrating web-based analysis has not been thoroughly conducted...
October 6, 2016: BMC Bioinformatics
Sarah A Weiss, Joseph Han, Farbod Darvishian, Jeremy Tchack, Sung Won Han, Karolina Malecek, Michelle Krogsgaard, Iman Osman, Judy Zhong
BACKGROUND: Age has been reported as an independent prognostic factor for melanoma-specific survival (MSS). We tested the hypothesis that age impacts the host anti-tumor immune response, accounting for age-specific survival outcomes in three unique melanoma patient cohorts. METHODS: We queried the U.S. population-based Surveillance, Epidemiology, and End Results Program (SEER), the prospective tertiary care hospital-based Interdisciplinary Melanoma Cooperative Group (IMCG) biorepository, and the Cancer Genome Atlas (TCGA) biospecimen database to test the association of patient age at time of melanoma diagnosis with clinicopathologic features and survival outcomes...
October 19, 2016: Journal of Translational Medicine
Heewon Park, Atsushi Niida, Seiya Imoto, Satoru Miyano
Driver gene selection is crucial to understand the heterogeneous system of cancer. To identity cancer driver genes, various statistical strategies have been proposed, especially the L1-type regularization methods have drawn a large amount of attention. However, the statistical approaches have been developed purely from algorithmic and statistical point, and the existing studies have applied the statistical approaches to genomic data analysis without consideration of biological knowledge. We consider a statistical strategy incorporating biological knowledge to identify cancer driver gene...
October 19, 2016: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
Iris J H van Vlodrop, Sophie C Joosten, Tim de Meyer, Kim M Smits, Leander Van Neste, Veerle Melotte, Marcella Baldewijns, Leo J Schouten, Piet A van den Brandt, Jana Jeschke, Joo Mi Yi, Kornel Schuebel, Nita Ahuja, James G Herman, Maureen Aarts, Fred T Bosman, Wim Van Criekinge, Manon van Engeland
PURPOSE: The currently used prognostic models for patients with non-metastatic clear cell renal cell carcinoma (ccRCC) are based on clinicopathological features and might be improved by adding molecular markers. Epigenetic alterations occur frequently in ccRCC and are promising biomarkers. The aim of this study is to identify prognostic promoter methylation markers for ccRCC. EXPERIMENTAL DESIGN: We integrated data generated by massive parallel sequencing of methyl-binding domain enriched DNA and microarray based RNA expression profiling of 5-aza-2'-deoxycytidine treated ccRCC cell lines to comprehensively characterize the ccRCC methylome...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jesus Gonzalez Bosquet, Andreea M Newtson, Rebecca K Chung, Kristina W Thiel, Timothy Ginader, Michael J Goodheart, Kimberly K Leslie, Brian J Smith
BACKGROUND: Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response...
October 19, 2016: Molecular Cancer
Francesca Bianchi, Michele Sommariva, Loris De Cecco, Tiziana Triulzi, Sandra Romero-Cordoba, Elda Tagliabue, Lucia Sfondrini, Andrea Balsari
The autoimmune regulator gene (AIRE) plays a fundamental role in tolerance by promoting the expression of tissue-specific antigens in medullary thymic epithelial cells (mTECs). Recently, AIRE expression was detected also in human keratinocytes and in tumors originating in stratified epithelia. Here, we tested whether AIRE is expressed in cancer cells. We analyzed AIRE expression in cancer cases from The Cancer Genome Atlas (TCGA) RNA-seq dataset and we found association with better outcome. AIRE protein expression was verified by immunohistochemistry in a cohort of 39 human breast cancer specimens and its prognostic relevance was confirmed in microarray-based gene expression dataset NKI-295 and KM-Plotter...
October 18, 2016: Cell Cycle
Schammim Ray Amith, Krista Marie Vincent, Jodi Marie Wilkinson, Lynne Marie Postovit, Larry Fliegel
Mounting evidence supports a major role for the Na(+)/H(+) exchanger NHE1 in cancer progression and metastasis. NHE1 is hyperactive at the onset of oncogenic transformation, resulting in intracellular alkalinization and extracellular microenvironmental acidification. These conditions promote invasion and facilitate metastasis. However, the signal pathways governing the regulation of exchanger activity are still unclear. This is especially important in the aggressively metastatic, triple-negative basal breast cancer subtype...
October 15, 2016: Cellular Signalling
Song Wu, Andrew Fesler, Jingfang Ju
AIM: To establish a connection between microRNA (miRNAs), circadian rhythm, and colorectal cancer patient survival. METHODS: Genomic and clinical data were extracted from The Cancer Genome Atlas (TCGA) colorectal cancer database, and the expression levels of candidate miRNAs and a set of circadian rhythm-related genes (Per1, Per2, Per3, Bmal1), and genes associated with chemosensitivity (thymidylate synthase, dihydrofolate reductase) were assessed for any correlations among their expression...
January 2016: Cancer Transl Med
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