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copy number variation AND lung cancer

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https://www.readbyqxmd.com/read/28627406/multi-omics-facilitated-variable-selection-in-cox-regression-model-for-cancer-prognosis-prediction
#1
Cong Liu, Xujun Wang, Georgi Z Genchev, Hui Lu
Motivation New developments in high-throughput genomic technologies have enabled the measurement of diverse types of omics biomarkers in a cost-efficient and clinically-feasible manner. Developing computational methods and tools for analysis and translation of such genomic data into clinically-relevant information is an ongoing and active area of investigation. For example, several studies have utilized an unsupervised learning framework to cluster patients by integrating omics data. Despite such recent advances, predicting cancer prognosis using integrated omics biomarkers remains a challenge...
June 13, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28548104/genomic-analysis-of-oesophageal-squamous-cell-carcinoma-identifies-alcohol-drinking-related-mutation-signature-and-genomic-alterations
#2
Jiang Chang, Wenle Tan, Zhiqiang Ling, Ruibin Xi, Mingming Shao, Mengjie Chen, Yingying Luo, Yanjie Zhao, Yun Liu, Xiancong Huang, Yuchao Xia, Jinlin Hu, Joel S Parker, David Marron, Qionghua Cui, Linna Peng, Jiahui Chu, Hongmin Li, Zhongli Du, Yaling Han, Wen Tan, Zhihua Liu, Qimin Zhan, Yun Li, Weimin Mao, Chen Wu, Dongxin Lin
Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28503373/analysis-of-genomic-variation-in-lung-adenocarcinoma-patients-revealed-the-critical-role-of-pi3k-complex
#3
Zhao Min Deng, Lin Liu, Wen Hai Qiu, Yong Qun Zhang, Hong Yan Zhong, Ping Liao, Yun Hong Wu
BACKGROUND: Molecularly targeted therapies improved survival status of some patients with lung adenocarcinoma, which accounts for 40% of all lung cancers, and in-depth study of gene alterations is important for the personalized treatment. METHODS: The legacy archive data of clinical information and genomic variations under the project TCGA Lung Adenocarcinoma were downloaded from the GDC Data Portal using R package TCGAbiolinks. The significantly aberrant copy number variants segments were figured out using GAIA...
2017: PeerJ
https://www.readbyqxmd.com/read/28468865/cell-free-dna-from-ascites-and-pleural-effusions-molecular-insights-into-genomic-aberrations-and-disease-biology
#4
Hatim Husain, David Nykin, Nam Bui, Daniel Quan, German Gomez, Brian Woodward, Sumathi Venkatapathy, Radha Duttagupta, Eric Fung, Scott M Lippman, Razelle Kurzrock
Collection of cell-free DNA (cfDNA) from the blood of individuals with cancer has permitted noninvasive tumor genome analysis. Detection and characterization of cfDNA in ascites and pleural effusions have not yet been reported. Herein, we analyzed cfDNA in the ascites and pleural effusions from six individuals with metastatic cancer. In all cases, cfDNA copy number variations (CNV) were discovered within the effusate. One individual had a relevant alteration with a high copy amplification in EGFR in a never smoker with lung cancer, who showed only MDM2 and CDK4 amplification in a prior tissue biopsy...
May 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28418179/copy-number-variation-increased-gene-expression-and-molecular-mechanisms-of-neurofascin-in-lung-cancer
#5
Johanna Samulin Erdem, Yke Jildouw Arnoldussen, Vidar Skaug, Aage Haugen, Shanbeh Zienolddiny
Metastasis and cell adhesion are key aspects of cancer progression. Neurofascin (NFASC) is a member of the immunoglobulin superfamily of adhesion molecules and, while studies on NFASC are inadequate, other members have been indicated pivotal roles in cancer progression and metastasis. This study aimed at increasing the knowledge on the involvement of adhesion molecules in lung cancer progression by studying the regulation and role of NFASC in non-small cell lung cancer (NSCLC). Here, copy number variations in the NFASC gene were analyzed in tumor and non-tumorous lung tissues of 204 NSCLC patients...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28389380/etumortype-an-algorithm-of-discriminating-cancer-types-for-circulating-tumor-cells-or-cell-free-dnas-in-blood
#6
Jinfeng Zou, Edwin Wang
With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs) of the cancer founding clone...
April 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28381877/the-genomic-dynamics-during-progression-of-lung-adenocarcinomas
#7
Bin Yang, Longhai Luo, Wen Luo, Yong Zhou, Chao Yang, Teng Xiong, Xiangchun Li, Xuan Meng, Lin Li, Xiaopin Zhang, Zhe Wang, Zhixin Wang
Intra-tumor heterogeneity is a big barrier to precision medicine. To explore the underlying clonal diversity in lung adenocarcinomas, we selected nine individuals with whole-genome sequencing data from primary and matched metastatic tumors as a cohort for study. Similar global pattern of arm-level copy number changes and large variations of somatic single-nucleotide variant between the primary and metastasis are observed in the majority of cases. Importantly, we found breakage-fusion-bridge (BFB) cycles acting as an important mechanism for underlying cancer gene amplification, such as amplification of CDK4, CDKN3 and FGFR1 in early stage...
April 6, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28379620/genome-wide-copy-number-variation-pattern-analysis-and-a-classification-signature-for-non-small-cell-lung-cancer
#8
Zhe-Wei Qiu, Jia-Hao Bi, Adi F Gazdar, Kai Song
The accurate classification of non-small cell lung carcinoma (NSCLC) into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) is essential for both clinical practice and lung cancer research. Although the standard WHO diagnosis of NSCLC on biopsy material is rapid and economic, more than 13% of NSCLC tumors in the USA are not further classified. The purpose of this study was to analyze the genome-wide pattern differences in copy number variations (CNVs) and to develop a CNV signature as an adjunct test for the routine histopathologic classification of NSCLCs...
July 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28371134/strandadvantage-test-for-early-line-and-advanced-stage-treatment-decisions-in-solid-tumors
#9
Manimala Sen, Shanmukh Katragadda, Aarthi Ravichandran, Gouri Deshpande, Minothi Parulekar, Swetha Nayanala, Vikram Vittal, Weiming Shen, Melanie Phooi Nee Yong, Jemima Jacob, Sravanthi Parchuru, Kalpana Dhanuskodi, Kenneth Eyring, Pooja Agrawal, Smita Agarwal, Ashwini Shanmugam, Satish Gupta, Divya Vishwanath, Kiran Kumari, Arun K Hariharan, Sai A Balaji, Qiaoling Liang, Belen Robolledo, Vijayashree Gauribidanur Raghavendrachar, Mohammed Oomer Farooque, Cary J Buresh, Preveen Ramamoorthy, Urvashi Bahadur, Kalyanasundaram Subramanian, Ramesh Hariharan, Vamsi Veeramachaneni, Satish Sankaran, Vaijayanti Gupta
Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report...
May 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28336923/integrative-analysis-of-multi-omics-data-reveals-distinct-impacts-of-ddb1-cul4-associated-factors-in-human-lung-adenocarcinomas
#10
Hong Yan, Lei Bi, Yunshan Wang, Xia Zhang, Zhibo Hou, Qian Wang, Antoine M Snijders, Jian-Hua Mao
Many DDB1-CUL4 associated factors (DCAFs) have been identified and serve as substrate receptors. Although the oncogenic role of CUL4A has been well established, specific DCAFs involved in cancer development remain largely unknown. Here we infer the potential impact of 19 well-defined DCAFs in human lung adenocarcinomas (LuADCs) using integrative omics analyses, and discover that mRNA levels of DTL, DCAF4, 12 and 13 are consistently elevated whereas VBRBP is reduced in LuADCs compared to normal lung tissues...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191267/single-cell-digital-polymerase-chain-reaction-on-self-priming-compartmentalization-chip
#11
Qiangyuan Zhu, Lin Qiu, Yanan Xu, Guang Li, Ying Mu
Single cell analysis provides a new framework for understanding biology and disease, however, an absolute quantification of single cell gene expression still faces many challenges. Microfluidic digital polymerase chain reaction (PCR) provides a unique method to absolutely quantify the single cell gene expression, but only limited devices are developed to analyze a single cell with detection variation. This paper describes a self-priming compartmentalization (SPC) microfluidic digital polymerase chain reaction chip being capable of performing single molecule amplification from single cell...
January 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28052041/non-malignant-respiratory-epithelial-cells-preferentially-proliferate-from-resected-non-small-cell-lung-cancer-specimens-cultured-under-conditionally-reprogrammed-conditions
#12
Boning Gao, Chunxian Huang, Kemp Kernstine, Vasiliki Pelekanou, Yuval Kluger, Tingting Jiang, Jennifer R Peters-Hall, Melissa Coquelin, Luc Girard, Wei Zhang, Kenneth Huffman, Dwight Oliver, Fumi Kinose, Eric Haura, Jamie K Teer, Uwe Rix, Anh T Le, Dara L Aisner, Marileila Varella-Garcia, Robert C Doebele, Kyle R Covington, Oliver A Hampton, Harsha V Doddapaneni, Joy C Jayaseelan, Jianhong Hu, David A Wheeler, Jerry W Shay, David L Rimm, Adi Gazdar, John D Minna
The "conditionally reprogrammed cells" (CRC) method, using a Rho kinase inhibitor and irradiated mouse fibroblast cells has been described for the efficient growth of cells from malignant and non-malignant samples from primary tumor and non-malignant sites. Using the CRC method, four institutions independently cultured tumor tissues from 48 non-small cell lung cancers (NSCLC, mostly from primary resected tumors) and 22 non-malignant lungs. We found that epithelial cells could be cultured from tumor and non-malignant lung...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/27896996/cerna-search-method-identified-a-met-activated-subgroup-among-egfr-dna-amplified-lung-adenocarcinoma-patients
#13
Halla Kabat, Leo Tunkle, Inhan Lee
Given the diverse molecular pathways involved in tumorigenesis, identifying subgroups among cancer patients is crucial in precision medicine. While most targeted therapies rely on DNA mutation status in tumors, responses to such therapies vary due to the many molecular processes involved in propagating DNA changes to proteins (which constitute the usual drug targets). Though RNA expressions have been extensively used to categorize tumors, identifying clinically important subgroups remains challenging given the difficulty of discerning subgroups within all possible RNA-RNA networks...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27896964/integrative-analysis-for-lung-adenocarcinoma-predicts-morphological-features-associated-with-genetic-variations
#14
Chao Wang, Hai Su, Lin Yang, Kun Huang
Lung cancer is one of the most deadly cancers and lung adenocarcinoma (LUAD) is the most common histological type of lung cancer. However, LUAD is highly heterogeneous due to genetic difference as well as phenotypic differences such as cellular and tissue morphology. In this paper, we systematically examine the relationships between histological features and gene transcription. Specifically, we calculated 283 morphological features from histology images for 201 LUAD patients from TCGA project and identified the morphological feature with strong correlation with patient outcome...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27863413/rictor-amplification-identifies-a-subgroup-in-small-cell-lung-cancer-and-predicts-response-to-drugs-targeting-mtor
#15
Nneha Sakre, Gary Wildey, Mohadese Behtaj, Adam Kresak, Michael Yang, Pingfu Fu, Afshin Dowlati
Small cell lung cancer (SCLC) is an aggressive cancer that represents ~15% of all lung cancers. Currently there are no targeted therapies to treat SCLC. Our genomic analysis of a metastatic SCLC cohort identified recurrent RICTOR amplification. Here, we examine the translational potential of this observation. RICTOR was the most frequently amplified gene observed (~14% patients), and co-amplified with FGF10 and IL7R on chromosome 5p13. RICTOR copy number variation correlated with RICTOR protein expression in SCLC cells...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27852032/complement-component-7-c7-a-potential-tumor-suppressor-is-correlated-with-tumor-progression-and-prognosis
#16
Lisha Ying, Fanrong Zhang, Xiaodan Pan, Kaiyan Chen, Nan Zhang, Jiaoyue Jin, Junzhou Wu, Jianguo Feng, Herbert Yu, Hongchuan Jin, Dan Su
Our previous study found copy number variation of chromosome fragment 5p13.1-13.3 might involve in the progression of ovarian cancer. In the current study, the alteration was validated and complement component 7 (C7), located on 5p13.1, was identified. To further explore the clinical value of C7 in tumors, 156 malignant, 22 borderline, 33 benign and 24 normal ovarian tissues, as well as 173 non-small cell lung cancer (NSCLC) tissues along with corresponding adjacent and normal tissues from the tissue bank of Zhejiang Cancer Hospital were collected...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27570645/gene-co-expression-analysis-predicts-genetic-variants-associated-with-drug-responsiveness-in-lung-cancer
#17
Sanaya Shroff, Jie Zhang, Kun Huang
Responsiveness to drugs is an important concern in designing personalized treatment for cancer patients. Currently genetic markers are often used to guide targeted therapy. However, deeper understanding of the molecular basis for drug responses and discovery of new predictive biomarkers for drug sensitivity are much needed. In this paper, we present a workflow for identifying condition-specific gene co-expression networks associated with responses to the tyrosine kinase inhibitor, Erlotinib, in lung adenocarcinoma cell lines using data from the Cancer Cell Line Encyclopedia by combining network mining and statistical analysis...
2016: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/27358486/an-aggressive-subtype-of-stage-i-lung-adenocarcinoma-with-molecular-and-prognostic-characteristics-typical-of-advanced-lung-cancers
#18
Elisa Dama, Valentina Melocchi, Fabio Dezi, Stefania Pirroni, Rose Mary Carletti, Daniela Brambilla, Monica Casiraghi, Giovanni Bertalot, Patrick Maisonneuve, Massimo Barberis, Giuseppe Viale, Manuela Vecchi, Lorenzo Spaggiari, Fabrizio Bianchi, Pier Paolo Di Fiore
PURPOSE: The National Lung Cancer Screening Trial has confirmed that lung cancer mortality can be reduced if tumors are diagnosed early, i.e. at stage I. However, a substantial fraction of stage I lung cancer patients still develop metastatic disease within 5 years from surgery. Prognostic biomarkers are therefore needed to identify patients at risk of an adverse outcome, who might benefit from multimodality treatment. EXPERIMENTAL DESIGN: We extensively validated a 10-gene prognostic signature in a cohort of 507 lung adenocarcinoma patients using formalin-fixed paraffin-embedded samples...
June 29, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27264345/copy-number-variation-of-mcl1-predicts-overall-survival-of-non-small-cell-lung-cancer-in-a-southern-chinese-population
#19
Jieyun Yin, Yangkai Li, Hao Zhao, Qin Qin, Xiaorong Li, Jiao Huang, Yun Shi, Shufang Gong, Li Liu, Xiangning Fu, Shaofa Nie, Sheng Wei
BCL2L1 and MCL1 are key anti-apoptotic genes, and critical for cancer progression. The prognostic values of BCL2L1 and MCL1 copy-number variations (CNVs) in non-small-cell lung cancer (NSCLC) remain largely unknown. Somatic CNVs in BCL2L1 and MCL1 genes were tested in tumor tissues from 516 NSCLC patients in southern China; afterward, survival analyses were conducted with overall survival (OS) as outcome. Additionally, the associations between CNVs and mRNA expression levels were explored using data from 986 NSCLC patients in the Cancer Genome Atlas project...
September 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27247954/capture-based-next-generation-sequencing-reveals-multiple-actionable-mutations-in-cancer-patients-failed-in-traditional-testing
#20
Jing Xie, Xiongxiong Lu, Xue Wu, Xiaoyi Lin, Chao Zhang, Xiaofang Huang, Zhili Chang, Xinjing Wang, Chenlei Wen, Xiaomei Tang, Minmin Shi, Qian Zhan, Hao Chen, Xiaxing Deng, Chenghong Peng, Hongwei Li, Yuan Fang, Yang Shao, Baiyong Shen
BACKGROUND: Targeted therapies including monoclonal antibodies and small molecule inhibitors have dramatically changed the treatment of cancer over past 10 years. Their therapeutic advantages are more tumor specific and with less side effects. For precisely tailoring available targeted therapies to each individual or a subset of cancer patients, next-generation sequencing (NGS) has been utilized as a promising diagnosis tool with its advantages of accuracy, sensitivity, and high throughput...
May 2016: Molecular Genetics & Genomic Medicine
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