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copy number variation AND lung cancer

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https://www.readbyqxmd.com/read/27896996/cerna-search-method-identified-a-met-activated-subgroup-among-egfr-dna-amplified-lung-adenocarcinoma-patients
#1
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
#2
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
#3
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...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27852032/complement-component-7-c7-a-potential-tumor-suppressor-is-correlated-with-tumor-progression-and-prognosis
#4
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...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27570645/gene-co-expression-analysis-predicts-genetic-variants-associated-with-drug-responsiveness-in-lung-cancer
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27218826/copy-number-changes-of-clinically-actionable-genes-in-melanoma-non-small-cell-lung-cancer-and-colorectal-cancer-a-survey-across-822-routine-diagnostic-cases
#9
Nicole Pfarr, Roland Penzel, Frederick Klauschen, Daniel Heim, Regine Brandt, Daniel Kazdal, Moritz Jesinghaus, Esther Herpel, Peter Schirmacher, Arne Warth, Wilko Weichert, Volker Endris, Albrecht Stenzinger
Targeted deep massive parallel sequencing has been implemented in routine molecular diagnostics for high-throughput genetic profiling of formalin-fixed paraffin-embedded (FFPE) cancer samples. This approach is widely used to interrogate simple somatic mutations but experience with the analysis of copy number variations (CNV) is limited. Here, we retrospectively analyzed CNV in 822 cancer cases (135 melanoma, 468 non-small cell lung cancers (NSCLC), 219 colorectal cancers (CRC)). We observed a decreasing frequency of CNV in clinically actionable genes from melanoma to NSCLC to CRC...
November 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27186987/inferring-rbp-mediated-regulation-in-lung-squamous-cell-carcinoma
#10
Atefeh Lafzi, Hilal Kazan
RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation of mRNAs. Dysregulations in RBP-mediated mechanisms have been found to be associated with many steps of cancer initiation and progression. Despite this, previous studies of gene expression in cancer have ignored the effect of RBPs. To this end, we developed a lasso regression model that predicts gene expression in cancer by incorporating RBP-mediated regulation as well as the effects of other well-studied factors such as copy-number variation, DNA methylation, TFs and miRNAs...
2016: PloS One
https://www.readbyqxmd.com/read/27105513/genetic-changes-of-non-small-cell-lung-cancer-under-neoadjuvant-therapy
#11
Arne Warth, Volker Endris, Albrecht Stenzinger, Roland Penzel, Alexander Harms, Thomas Duell, Amir Abdollahi, Michael Lindner, Peter Schirmacher, Thomas Muley, Hendrik Dienemann, Ludger Fink, Alicia Morresi-Hauf, Nicole Pfarr, Wilko Weichert
BACKGROUND: Large scale sequencing efforts defined common molecular alterations in non-small cell lung cancer (NSCLC) and revealed potentially druggable mutations. Yet, systematic data on the changes of the respective molecular profiles under standard therapy in NSCLC are limited. RESULTS: 14 out of 68 observed coding mutations (21%) and 6 out of 33 (18%) copy number variations (CNV) were lost or gained during therapy. Mutational and CNV changes clustered in 6/37 (16%) and 3/37 (8%) patients...
May 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27029813/multivariate-models-from-rna-seq-snvs-yield-candidate-molecular-targets-for-biomarker-discovery-snv-da
#12
Matt R Paul, Nicholas P Levitt, David E Moore, Patricia M Watson, Robert C Wilson, Chadrick E Denlinger, Dennis K Watson, Paul E Anderson
BACKGROUND: It has recently been shown that significant and accurate single nucleotide variants (SNVs) can be reliably called from RNA-Seq data. These may provide another source of features for multivariate predictive modeling of disease phenotype for the prioritization of candidate biomarkers. The continuous nature of SNV allele fraction features allows the concurrent investigation of several genomic phenomena, including allele specific expression, clonal expansion and/or deletion, and copy number variation...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27026619/impact-a-whole-exome-sequencing-analysis-pipeline-for-integrating-molecular-profiles-with-actionable-therapeutics-in-clinical-samples
#13
Jennifer Hintzsche, Jihye Kim, Vinod Yadav, Carol Amato, Steven E Robinson, Eric Seelenfreund, Yiqun Shellman, Joshua Wisell, Allison Applegate, Martin McCarter, Neil Box, John Tentler, Subhajyoti De, William A Robinson, Aik Choon Tan
OBJECTIVE: Currently, there is a disconnect between finding a patient's relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics. METHODS AND MATERIALS: The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity...
July 2016: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/26936516/a-targeted-next-generation-sequencing-method-for-identifying-clinically-relevant-mutation-profiles-in-lung-adenocarcinoma
#14
Di Shao, Yongping Lin, Jilong Liu, Liang Wan, Zu Liu, Shaomin Cheng, Lingna Fei, Rongqing Deng, Jian Wang, Xi Chen, Liping Liu, Xia Gu, Wenhua Liang, Ping He, Jun Wang, Mingzhi Ye, Jianxing He
Molecular profiling of lung cancer has become essential for prediction of an individual's response to targeted therapies. Next-generation sequencing (NGS) is a promising technique for routine diagnostics, but has not been sufficiently evaluated in terms of feasibility, reliability, cost and capacity with routine diagnostic formalin-fixed, paraffin-embedded (FFPE) materials. Here, we report the validation and application of a test based on Ion Proton technology for the rapid characterisation of single nucleotide variations (SNVs), short insertions and deletions (InDels), copy number variations (CNVs), and gene rearrangements in 145 genes with FFPE clinical specimens...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26880400/chromosomal-microarray-provides-enhanced-targetable-gene-aberration-detection-when-paired-with-next-generation-sequencing-panel-in-profiling-lung-and-colorectal-tumors
#15
S Mukherjee, Z Ma, S Wheeler, M Sathanoori, C Coldren, J L Prescott, N Kozyr, M Bouzyk, M Correll, H Ho, P K Chandra, P A Lennon
The development of targeted therapies based on specific genomic alterations has altered the treatment and management of lung and colorectal cancers. Chromosomal microarray (CMA) has allowed identification of copy number variations (CNVs) in lung and colorectal cancers in great detail, and next-generation sequencing (NGS) is used extensively to analyze the genome of cancers for molecular subtyping and use of molecularly guided therapies. The main objective of this study was to evaluate the utility of combining CMA and NGS for a comprehensive genomic assessment of lung and colorectal adenocarcinomas, especially for detecting drug targets...
April 2016: Cancer Genetics
https://www.readbyqxmd.com/read/26818358/genetic-determinants-of-cyp2a6-activity-across-racial-ethnic-groups-with-different-risks-of-lung-cancer-and-effect-on-their-smoking-intensity
#16
Sungshim L Park, Maarit I Tiirikainen, Yesha M Patel, Lynne R Wilkens, Daniel O Stram, Loic Le Marchand, Sharon E Murphy
Genetic variation in cytochrome P450 2A6 (CYP2A6) gene is the primary contributor to the intraindividual and interindividual differences in nicotine metabolism and has been found to influence smoking intensity. However, no study has evaluated the relationship between CYP2A6 genetic variants and the CYP2A6 activity ratio (total 3-hydroxycotinine/cotinine) and their influence on smoking intensity [total nicotine equivalents (TNE)], across five racial/ethnic groups found to have disparate rates of lung cancer...
March 2016: Carcinogenesis
https://www.readbyqxmd.com/read/26803564/-lung-cancer-molecular-testing-what-role-for-next-generation-sequencing-and-circulating-tumor-dna
#17
Nicolas Pécuchet, Antoine Legras, Pierre Laurent-Puig, Hélène Blons
Molecular screening has become a standard of care for patients with advanced cancers and impacts on how to treat a patient. Advances in genomic technologies with the development of high throughput sequencing methods will certainly improve the possibilities to access a more accurate molecular diagnosis and to go beyond the identification of validated targets as a large number of genes can be screened for actionable changes. Moreover, accurate high throughput testing may help tumor classification in terms of prognosis and drug sensitivity...
January 2016: Annales de Pathologie
https://www.readbyqxmd.com/read/26780934/mutations-in-tp53-increase-the-risk-of-sox2-copy-number-alterations-and-silencing-of-tp53-reduces-sox2-expression-in-non-small-cell-lung-cancer
#18
Johanna Samulin Erdem, Vidar Skaug, Per Bakke, Amund Gulsvik, Aage Haugen, Shanbeh Zienolddiny
BACKGROUND: Amplifications of the transcription factor, SRY (sex determining region Y)-box 2 (SOX2), are common in non-small cell lung cancer (NSCLC). SOX2 signaling is important in maintaining the stem cell-like phenotype of cancer cells and contributes to the pathogenesis of lung cancer. TP53 is known to inhibit gene amplifications and to repress many stem cell-associated genes following DNA damage. The aim of this study was to investigate if TP53 mutational status affected SOX2 copy number variation and gene expression in early-stage NSCLC patients; moreover, to assess if TP53 regulates SOX2 expression in human lung cancer cells...
January 19, 2016: BMC Cancer
https://www.readbyqxmd.com/read/26510534/changes-in-correlation-between-promoter-methylation-and-gene-expression-in-cancer
#19
Matahi Moarii, Valentina Boeva, Jean-Philippe Vert, Fabien Reyal
BACKGROUND: Methylation of high-density CpG regions known as CpG Islands (CGIs) has been widely described as a mechanism associated with gene expression regulation. Aberrant promoter methylation is considered a hallmark of cancer involved in silencing of tumor suppressor genes and activation of oncogenes. However, recent studies have also challenged the simple model of gene expression control by promoter methylation in cancer, and the precise mechanism of and role played by changes in DNA methylation in carcinogenesis remains elusive...
October 28, 2015: BMC Genomics
https://www.readbyqxmd.com/read/26318634/the-impact-of-the-cancer-genome-atlas-on-lung-cancer
#20
REVIEW
Jeremy T-H Chang, Yee Ming Lee, R Stephanie Huang
The Cancer Genome Atlas (TCGA) has profiled more than 10,000 samples derived from 33 types of cancer to date, with the goal of improving our understanding of the molecular basis of cancer and advancing our ability to diagnose, treat, and prevent cancer. This review focuses on lung cancer as it is the leading cause of cancer-related mortality worldwide in both men and women. Particularly, non-small cell lung cancers (including lung adenocarcinoma and lung squamous cell carcinoma) were evaluated. Our goal was to demonstrate the impact of TCGA on lung cancer research under 4 themes: diagnostic markers, disease progression markers, novel therapeutic targets, and novel tools...
December 2015: Translational Research: the Journal of Laboratory and Clinical Medicine
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