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Integrative genomics cancer

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https://www.readbyqxmd.com/read/29924316/genome-wide-association-study-of-familial-lung-cancer
#1
Jinyoung Byun, Ann G Schwartz, Christine Lusk, Angela S Wenzlaff, Mariza de Andrade, Diptasri Mandal, Colette Gaba, Ping Yang, Ming You, Elena Y Kupert, Marshall W Anderson, Younghun Han, Yafang Li, David Qian, Adrienne Stilp, Cathy Laurie, Sarah Nelson, Wenying Zheng, Rayjean J Hung, Valerie Gaborieau, James Mckay, Paul Brennan, Neil E Caporaso, Maria Teresa Landi, Xifeng Wu, John R McLaughlin, Yonathan Brhane, Yohan Bossé, Susan M Pinney, Joan E Bailey-Wilson, Christopher I Amos
To identify genetic variation associated with lung cancer risk, we performed a genome-wide association analysis of 685 lung cancer cases that had a family history of two or more first or second degree relatives compared with 744 controls without lung cancer that were genotyped on an Illumina Human OmniExpressExome-8v1 array. To ensure robust results, we further evaluated these findings using data from six additional studies that were assembled through the Transdisciplinary Research on Cancer of the Lung Consortium comprising 1,993 familial cases and 33,690 controls...
June 19, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29923223/orchestrating-a-biomarker-panel-with-lncrnas-and-mrnas-for-predicting-survival-in-pancreatic-ductal-adenocarcinoma
#2
Yingcheng Wu, Jinhuan Wei, Yue Ming, Zhanghao Chen, Jinzhong Yu, Renfang Mao, Hao Chen, Guoxiong Zhou, Yihui Fan
The low survival of patients with pancreatic ductal adenocarcinoma (PDAC) makes the treatment of this disease one of the most challenging task in modern medicine. Here, by mining a large-scale cancer genome atlas data set of pancreatic cancer tissues, we identified 21 long noncoding RNAs (lncRNAs) that significantly associated with overall survival in patients with PDAC (P < .01). Further analysis revealed that 8 lncRNAs turned out to be independently correlated with patients' overall survival, and the risk score could be calculated based on their expression...
June 20, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29921511/the-lncrna-snhg3-regulates-energy-metabolism-of-ovarian-cancer-by-an-analysis-of-mitochondrial-proteomes
#3
Na Li, Xiaohan Zhan, Xianquan Zhan
BACKGROUND: Malignant tumors are heterogeneous diseases characterized by different metabolic phenotypes. These were revealed by Warburg effect and reverse Warburg effect phenotypes. However, the molecular mechanism remains largely unknown. METHODS: Isobaric tag for relative and absolute quantification (iTRAQ) proteomics was used to identify mitochondrial differentially expressed proteins (DEPs) of ovarian cancers relative to controls, followed by bioinformatic analysis...
June 16, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29915361/amp-kinase-promotes-glioblastoma-bioenergetics-and-tumour-growth
#4
Rishi Raj Chhipa, Qiang Fan, Jane Anderson, Ranjithmenon Muraleedharan, Yan Huang, Georgianne Ciraolo, Xiaoting Chen, Ronald Waclaw, Lionel M Chow, Zaza Khuchua, Matthew Kofron, Matthew T Weirauch, Ady Kendler, Christopher McPherson, Nancy Ratner, Ichiro Nakano, Nupur Dasgupta, Kakajan Komurov, Biplab Dasgupta
Stress is integral to tumour evolution, and cancer cell survival depends on stress management. We found that cancer-associated stress chronically activates the bioenergetic sensor AMP kinase (AMPK) and, to survive, tumour cells hijack an AMPK-regulated stress response pathway conserved in normal cells. Analysis of The Cancer Genome Atlas data revealed that AMPK isoforms are highly expressed in the lethal human cancer glioblastoma (GBM). We show that AMPK inhibition reduces viability of patient-derived GBM stem cells (GSCs) and tumours...
June 18, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29911110/optimization-of-a-microfluidics-based-next-generation-sequencing-assay-for-clinical-oncology-diagnostics
#5
Christine Henzler, Matthew Schomaker, Rendong Yang, Aaron P Lambert, Rebecca LaRue, Robyn Kincaid, Kenneth Beckman, Teresa Kemmer, Jon Wilson, Sophia Yohe, Bharat Thyagarajan, Andrew C Nelson
Background: Massively parallel, or next-generation, sequencing is a powerful technique for the assessment of somatic genomic alterations in cancer samples. Numerous gene targets can be interrogated simultaneously with a high degree of sensitivity. The clinical standard of care for many advanced solid and hematologic malignancies currently requires mutation analysis of several genes in the front-line setting, making focused next generation sequencing (NGS) assays an effective tool for clinical molecular diagnostic laboratories...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911109/prostate-cancer-in-the-era-of-omic-medicine-recognizing-the-importance-of-dna-damage-repair-pathways
#6
REVIEW
Zachary Kornberg, Jonathan Chou, Felix Y Feng, Charles J Ryan
Data from recent high-throughput studies analyzing local and advanced prostate cancer have revealed an incredible amount of biological diversity, which has led to the classification of distinct molecular tumor subtypes. While integrating prostate cancer genomics with clinical medicine is still at its infancy, new approaches to treat prostate cancer are well underway and being studied. With the recognition that DNA damage repair (DDR) mutations play an important role in the pathogenesis of this disease, clinicians can begin to utilize genomic information in complex treatment decisions for prostate cancer patients...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29907802/evaluating-the-role-of-public-health-in-implementation-of-genomics-related-recommendations-a-case-study-of-hereditary-cancers-using-the-cdc-science-impact-framework
#7
REVIEW
Ridgely Fisk Green, Mary Ari, Katherine Kolor, W David Dotson, Scott Bowen, Nancy Habarta, Juan L Rodriguez, Lisa C Richardson, Muin J Khoury
Public health plays an important role in ensuring access to interventions that can prevent disease, including the implementation of evidence-based genomic recommendations. We used the Centers for Disease Control and Prevention (CDC) Science Impact Framework to trace the impact of public health activities and partnerships on the implementation of the 2009 Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Lynch Syndrome screening recommendation and the 2005 and 2013 United States Preventive Services Task Force (USPSTF) BRCA1 and BRCA2 testing recommendations...
June 15, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29907296/surface-enhanced-raman-spectroscopy-based-immunosensor-for-ultrasensitive-and-selective-detection-of-wild-type-p53-and-mutant-p53-r175h
#8
Anna Rita Bizzarri, Ilaria Moscetti, Salvatore Cannistraro
p53 is a powerful transcription factor playing a pivotal role in the prevention of cancer development and in maintaining genome integrity. This oncosuppressor is found to be functionally inactivated by mutations in many human tumors. Accordingly, wild type p53 and its oncogenic mutants represent valuable cancer biomarkers for diagnostic and prognostic purposes. We developed a highly sensitive biosensor, based on Surface Enhanced Raman Spectroscopy, for detection of wild type p53 and of p53R175H , which is one of the most frequent tumor-associated mutants of p53...
October 31, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29906450/inactivation-of-cdk12-delineates-a-distinct-immunogenic-class-of-advanced-prostate-cancer
#9
Yi-Mi Wu, Marcin Cieślik, Robert J Lonigro, Pankaj Vats, Melissa A Reimers, Xuhong Cao, Yu Ning, Lisha Wang, Lakshmi P Kunju, Navonil de Sarkar, Elisabeth I Heath, Jonathan Chou, Felix Y Feng, Peter S Nelson, Johann S de Bono, Weiping Zou, Bruce Montgomery, Ajjai Alva, Dan R Robinson, Arul M Chinnaiyan
Using integrative genomic analysis of 360 metastatic castration-resistant prostate cancer (mCRPC) samples, we identified a novel subtype of prostate cancer typified by biallelic loss of CDK12 that is mutually exclusive with tumors driven by DNA repair deficiency, ETS fusions, and SPOP mutations. CDK12 loss is enriched in mCRPC relative to clinically localized disease and characterized by focal tandem duplications (FTDs) that lead to increased gene fusions and marked differential gene expression. FTDs associated with CDK12 loss result in highly recurrent gains at loci of genes involved in the cell cycle and DNA replication...
June 14, 2018: Cell
https://www.readbyqxmd.com/read/29898407/integrated-molecular-characterization-of-testicular-germ-cell-tumors
#10
Hui Shen, Juliann Shih, Daniel P Hollern, Linghua Wang, Reanne Bowlby, Satish K Tickoo, Vésteinn Thorsson, Andrew J Mungall, Yulia Newton, Apurva M Hegde, Joshua Armenia, Francisco Sánchez-Vega, John Pluta, Louise C Pyle, Rohit Mehra, Victor E Reuter, Guilherme Godoy, Jeffrey Jones, Carl S Shelley, Darren R Feldman, Daniel O Vidal, Davor Lessel, Tomislav Kulis, Flavio M Cárcano, Kristen M Leraas, Tara M Lichtenberg, Denise Brooks, Andrew D Cherniack, Juok Cho, David I Heiman, Katayoon Kasaian, Minwei Liu, Michael S Noble, Liu Xi, Hailei Zhang, Wanding Zhou, Jean C ZenKlusen, Carolyn M Hutter, Ina Felau, Jiashan Zhang, Nikolaus Schultz, Gad Getz, Matthew Meyerson, Joshua M Stuart, Rehan Akbani, David A Wheeler, Peter W Laird, Katherine L Nathanson, Victoria K Cortessis, Katherine A Hoadley
We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma...
June 12, 2018: Cell Reports
https://www.readbyqxmd.com/read/29897425/integrated-multi-omic-predictors-for-ovarian-cancer-survival
#11
A Fu, H R Chang, Z F Zhang
Increasingly affordable high-throughput molecular profiling technologies have made feasible the measurement of omics-wide interindividual variations for the purposes of predicting cancer prognosis. While multiple types of genetic, epigenetic, and expression changes have been implicated in ovarian cancer, existing prognostic biomarker strategies are constrained to analyzing single classes of molecular variations. The extra predictive power afforded by the integration of multiple omics types remains largely unexplored...
April 20, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29897414/conics-integrates-scrna-seq-with-dna-sequencing-to-map-gene-expression-to-tumor-sub-clones
#12
Sören Müller, Ara Cho, Siyuan J Liu, Daniel A Lim, Aaron Diaz
Motivation: Single-cell RNA-sequencing (scRNA-seq) has enabled studies of tissue composition at unprecedented resolution. However, the application of scRNA-seq to clinical cancer samples has been limited, partly due to a lack of scRNA-seq algorithms that integrate genomic mutation data. Results: To address this, we present. CONICS: COpy-Number analysis In single-Cell RNA-Sequencing. CONICS is a software tool for mapping gene expression from scRNA-seq to tumor clones and phylogenies, with routines enabling: the quantitation of copy-number alterations in scRNA-seq, robust separation of neoplastic cells from tumor-infiltrating stroma, inter-clone differential-expression analysis, and intra-clone co-expression analysis...
April 20, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29897144/surveillance-of-retroelement-expression-and-nucleic-acid-immunity-by-histone-methyltransferase-setdb1
#13
REVIEW
Yong-Kook Kang
In human cancers, histone methyltransferase SETDB1 (SET domain, bifurcated 1) is frequently overexpressed but its significance in carcinogenesis remains elusive. A recent study shows that SETDB1 downregulation induces de-repression of retroelements and innate immunity in cancer cells. The possibility of SETDB1 functioning as a surveillant of retroelement expression is discussed in this study: the cytoplasmic presence of retroelement-derived nucleic acids (RdNAs) drives SETDB1 into the nucleus by the RNA-interference route, rendering the corresponding retroelement transcriptionally inert...
June 13, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29896967/multilevel-omic-data-clustering-reveals-variable-contribution-of-methylator-phenotype-to-integrative-cancer-subtypes
#14
Pawel Karpinski, Arpad Patai, Wojciech Hap, Wojciech Kielan, Izabela Laczmanska, Maria Malgorzata Sasiadek
AIM: We aimed to assess to what extent CpG island methylator phenotype (CIMP) contributes to cancer subtypes obtained by multilevel omic data analysis. MATERIALS & METHODS: 16 The Cancer Genome Atlas datasets encompassing three data layers in 4688 tumor samples were analyzed. We identified cancer integrative subtypes (ISs) by the use of similarity network fusion and consensus clustering. CIMP high (CIMP-H) associated ISs were profiled by gene sets and transcriptional regulators enrichment analysis...
June 13, 2018: Epigenomics
https://www.readbyqxmd.com/read/29896679/gastritis-infection-cancer-sequence-of-epstein-barr-virus-associated-gastric-cancer
#15
Masashi Fukayama, Akiko Kunita, Atsushi Kaneda
Epstein-Barr virus-associated gastric cancer (EBVaGC) is a representative EBV-infected epithelial neoplasm, which is now included as one of the four subtypes of The Cancer Genome Atlas molecular classification of gastric cancer. In this review, we portray a gastritis-infection-cancer sequence of EBVaGC. This virus-associated type of gastric cancer demonstrates clonal growth of EBV-infected epithelial cells within the mucosa of atrophic gastritis. Its core molecular abnormality is the EBV-specific hyper-epigenotype of CpG island promoter methylation, which induces silencing of tumor suppressor genes...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29896284/development-of-a-three-gene-prognostic-signature-for-hepatitis-b-virus-associated-hepatocellular-carcinoma-based-on-integrated-transcriptomic-analysis
#16
Yao Yang, Qian Lu, Xuejun Shao, Banghui Mo, Xuqiang Nie, Wei Liu, Xianhua Chen, Yuan Tang, Youcai Deng, Jun Yan
Integration of public genome-wide gene expression data together with Cox regression analysis is a powerful weapon to identify new prognostic gene signatures for cancer diagnosis and prognosis. Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC), however, it remains largely unknown about the specific gene prognostic signature of HBV-associated HCC. Using Robust Rank Aggreg (RRA) method to integrate seven whole genome expression datasets, we identified 82 up-regulated genes and 577 down-regulated genes in HBV-associated HCC patients...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29896199/integrated-expression-profiles-analysis-reveals-correlations-between-the-il-33-st2-axis-and-cd8-t-cells-regulatory-t-cells-and-myeloid-derived-suppressor-cells-in-soft-tissue-sarcoma
#17
Huoying Chen, Yao Chen, Hongbo Liu, Yi Que, Xing Zhang, Fang Zheng
Soft tissue sarcoma (STS) is a rare solid malignant cancer, and there are few effective treatment options for advanced disease. Cancer immunotherapy is a promising new strategy for STS treatment. IL-33 is a candidate cytokine for immunotherapy that can activate T lymphocytes and modulate antitumor immunity in some cancers. However, the expression and biological role of IL-33 in STS are poorly understood. In this study, we found that the expression of IL-33 and its receptor ST2 was decreased in STS using real-time PCR assays...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29895854/understanding-the-potential-of-state-based-public-health-genomics-programs-to-mitigate-disparities-in-access-to-clinical-genetic-services
#18
Laura Senier, Catherine Tan, Leandra Smollin, Rachael Lee
PURPOSE: State health agencies (SHAs) have developed public health genomics (PHG) programs that play an instrumental role in advancing precision public health, but there is limited research on their approaches. This study examines how PHG programs attempt to mitigate or forestall health disparities and inequities in the utilization of genomic medicine. METHODS: We compared PHG programs in three states: Connecticut, Michigan, and Utah. We analyzed 85 in-depth interviews with SHA internal and external collaborators and program documents...
June 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29895125/clinical-efficacy-of-p16-ki-67-dual-stained-cervical-cytology-in-secondary-prevention-of-cervical-cancer
#19
Aleksander Celewicz, Marta Celewicz, Małgorzata Wężowska, Anita Chudecka-Głaz, Janusz Menkiszak, Elzbieta Urasińska
Cervical cancer is the third most common malignant neoplasm in women worldwide. HPV infection is the necessary factor for the cancer to develop. HPV DNA can be integrated into the genome of squamous epithelium and cause transcription of the viral oncoproteins and development of invasive cancer within 15-20 years. We assessed ICC co-expression of p16/Ki-67 proteins in smears collected from the uterine cervix and the association between p16/Ki-67 co-expression and cytologic and histologic results. Samples were collected from 93 women using liquid based cytology (LBC)...
2018: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
https://www.readbyqxmd.com/read/29891880/a-theory-informed-systematic-review-of-clinicians-genetic-testing-practices
#20
REVIEW
Jean L Paul, Hanna Leslie, Alison H Trainer, Clara Gaff
This systematic literature review investigates factors impacting on clinicians' decisions to offer genetic tests in their practice, and maps them to a theoretical behaviour change framework. Better understanding of these factors will inform the design of effective interventions to integrate genomics tests into clinical care. We conducted a narrative synthesis of empirical research of medical specialists' perspectives on and experiences of offering genetic tests to their patients. This review was based upon the PRISMA statement and guidelines for reviewing qualitative research...
June 11, 2018: European Journal of Human Genetics: EJHG
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