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copy number variation AND lung cancer

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https://www.readbyqxmd.com/read/29322935/classifying-cancer-genome-aberrations-by-their-mutually-exclusive-effects-on-transcription
#1
Jonathan B Dayton, Stephen R Piccolo
BACKGROUND: Malignant tumors are typically caused by a conglomeration of genomic aberrations-including point mutations, small insertions, small deletions, and large copy-number variations. In some cases, specific chemotherapies and targeted drug treatments are effective against tumors that harbor certain genomic aberrations. However, predictive aberrations (biomarkers) have not been identified for many tumor types and treatments. One way to address this problem is to examine the downstream, transcriptional effects of genomic aberrations and to identify characteristic patterns...
December 21, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29178066/mitochondrial-dna-in-lung-cancer
#2
Fangming Liu, David E Sanin, Xiangdong Wang
Mitochondrial DNA (mtDNA) variations are increasingly discovered and expected to be potential biomarkers to monitor severity, duration, stage, response to therapy, and prognosis in patients with lung cancer. The present article illustrates alterations of mtDNA in lung cancer, including alterations of mtDNA copy number and sequence mutations, as well as their possible mechanisms for carcinogenesis and development of lung cancer. The clear and comprehensive relationships between mtDNA variations and lung cancer are to be further confirmed to benefit effective strategies for lung cancer diagnosis and therapy...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29054765/characterization-of-germline-mutations-in-familial-lung-cancer-from-the-chinese-population
#3
Madiha Kanwal, Xiao-Jie Ding, Zhans-Han Ma, Lian-Wei Li, Ping Wang, Ying Chen, Yun-Chao Huang, Yi Cao
Compared with numerous studies of somatic mutations using sporadic lung cancer, the research into germline mutations using familial lung cancer (FLC) is limited. In the present study, we used FLC samples obtained from the Chinese population in highly air-polluted regions to screen for novel germline mutations in lung cancer. Through a whole genome sequencing (WGS) analysis of the nine subjects (four lung cancer patients and five normal family members of FLC), we obtained a whole genome dataset of DNA alterations in FLC samples...
October 17, 2017: Gene
https://www.readbyqxmd.com/read/29039585/identification-of-genome-variations-in-patients-with-lung-adenocarcinoma-using-whole-genome-re%C3%A2-sequencing
#4
Guiyuan Li, Yunqing Mei, Fan Yang, Shengming Yi, Lemin Wang
Lung adenocarcinoma is one of the types of non‑small cell lung carcinoma, which tends to be treated with surgical therapy rather than radiation therapy. It occurs in smokers and non‑smokers, and is the most common form of lung cancer among non‑smokers and women. Gene rearrangements, including ALK, ROS1 and RET, and gene mutations, including epidermal growth factor receptor (EGFR), HER2, Kristen rat sarcoma viral oncogene homolog, BRAF, phosphoinositide‑3‑kinase, catalytic, α polypeptide and MET, have been identified in lung adenocarcinoma, which enable targeted therapy in lung adenocarcinoma, for example erlotinib, gefitinib and afatinib, which are EGFR inhibitors...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28960030/gab2-amplification-in-squamous-cell-lung-cancer-of-non-smokers
#5
Yu Rang Park, Soo Hyeon Bae, Wonjun Ji, Eul Ju Seo, Jae Cheol Lee, Hyeong Ryul Kim, Se Jin Jang, Chang Min Choi
Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015...
November 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28947568/discrimination-of-germline-egfr-t790m-mutations-in-plasma-cell-free-dna-allows-study-of-prevalence-across-31-414-cancer-patients
#6
Yuebi Hu, Ryan S Alden, Justin I Odegaard, Stephen R Fairclough, Ruthia Chen, Jennifer Heng, Nora Feeney, Rebecca Nagy, Jayshree Shah, Bryan Ulrich, Martin Gutierrez, Richard B Lanman, Judy E Garber, Cloud P Paweletz, Geoffrey R Oxnard
PURPOSE: Plasma cell-free DNA (cfDNA) analysis is increasingly used clinically for cancer genotyping, but may lead to incidental identification of germline risk alleles. We studied EGFR T790M mutations in non-small cell lung cancer (NSCLC) toward the aim of discriminating germline and cancer-derived variants within cfDNA. EXPERIMENTAL DESIGN: Patients with EGFR-mutant NSCLC, some with known germline EGFR T790M, underwent plasma genotyping. Separately, deidentified genomic data and buffy coat specimens from a clinical plasma next-generation sequencing (NGS) laboratory were reviewed and tested...
September 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28880866/ribosomal-dna-copy-number-amplification-and-loss-in-human-cancers-is-linked-to-tumor-genetic-context-nucleolus-activity-and-proliferation
#7
Meng Wang, Bernardo Lemos
Ribosomal RNAs (rRNAs) are transcribed from two multicopy DNA arrays: the 5S ribosomal DNA (rDNA) array residing in a single human autosome and the 45S rDNA array residing in five human autosomes. The arrays are among the most variable segments of the genome, exhibit concerted copy number variation (cCNV), encode essential components of the ribosome, and modulate global gene expression. Here we combined whole genome data from >700 tumors and paired normal tissues to provide a portrait of rDNA variation in human tissues and cancers of diverse mutational signatures, including stomach and lung adenocarcinomas, ovarian cancers, and others of the TCGA panel...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28627406/multi-omics-facilitated-variable-selection-in-cox-regression-model-for-cancer-prognosis-prediction
#8
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...
July 15, 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
#9
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
#10
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
#11
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
#12
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...
September 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
#13
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
#14
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...
August 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
2017: Pacific Symposium on Biocomputing
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