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whole genome sequencing AND lung cancer

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https://www.readbyqxmd.com/read/29748005/genomic-alterations-of-plasma-cell-free-dnas-in-small-cell-lung-cancer-and-their-clinical-relevance
#1
Meijun Du, Jonathan Thompson, Hannah Fisher, Peng Zhang, Chiang-Ching Huang, Liang Wang
OBJECTIVES: To identify genomic variations in cell-free DNA (cfDNA) and evaluate their clinical utility in small cell lung cancer (SCLC). MATERIALS AND METHODS: We performed whole genome sequencing using plasma cfDNAs derived from 24 SCLC patients for copy number variation (CNV) analysis, and targeted sequencing using 17 pairs of plasma cfDNA and their matched gDNA for mutation analysis. We defined somatic mutations by comparing cfDNA to its matched gDNA with 5% variant alleles as the cutoff for mutation calls...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29736260/mutation-load-estimation-model-as-a-predictor-of-the-response-to-cancer-immunotherapy
#2
Guan-Yi Lyu, Yu-Hsuan Yeh, Yi-Chen Yeh, Yu-Chao Wang
The determination of the mutation load, a total number of nonsynonymous point mutations, by whole-exome sequencing was shown to be useful in predicting the treatment responses to cancer immunotherapy. However, this technique is expensive and time-consuming, which hampers its application in clinical practice. Therefore, the objective of this study was to construct a mutation load estimation model for lung adenocarcinoma, using a small set of genes, as a predictor of the immunotherapy treatment response. Using the somatic mutation data downloaded from The Cancer Genome Atlas (TCGA) database, a computational framework was developed...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29720381/whole-exome-and-transcriptome-analyses-integrated-with-microenvironmental-immune-signatures-of-lung-squamous-cell-carcinoma
#3
Jeong-Sun Seo, Ji Won Lee, Ahreum Kim, Jong-Yeon Shin, Yoo Jin Jung, Sae Bom Lee, Yoon Ho Kim, Samina Park, Hyun Joo Lee, In-Kyu Park, Chang Hyun Kang, Ji-Young Yun, Jihye Kim, Young T Kim
The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions. We sequenced whole exomes and RNA from 101 tumors and matched noncancer control Korean samples...
May 2, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29667179/characteristics-of-genomic-alterations-of-lung-adenocarcinoma-in-young-never-smokers
#4
Wenxin Luo, Panwen Tian, Yue Wang, Heng Xu, Lu Chen, Chao Tang, Yang Shu, Shouyue Zhang, Zhoufeng Wang, Jun Zhang, Li Zhang, Lili Jiang, Lunxu Liu, Guowei Che, Chenglin Guo, Hong Zhang, Jiali Wang, Weimin Li
Non-small cell lung cancer (NSCLC) has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. While never-smoker patients with NSCLC have been well studied through next generation sequencing, we have yet to recognize the potentially unique molecular features of young never-smoker patients with NSCLC. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never-smoker Chinese patients, who were diagnosed with lung adenocarcinoma (LUAD) at 45 years or younger...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29660202/molecular-biomarkers-for-uterine-leiomyosarcoma-and-endometrial-stromal-sarcoma
#5
REVIEW
Hideaki Tsuyoshi, Yoshio Yoshida
Uterine leiomyosarcoma (u{\hyphen}LMS) and endometrial stromal sarcoma (ESS) are among the most frequent soft tissue sarcomas, which, in adults, lead to fatal lung metastases and have an extremely poor prognosis. Due to their rarity and heterogeneity, there are no suitable biomarkers for diagnosis and prognosis, though some biomarker candidates have appeared. Recently, The Cancer Genome Atlas (TCGA) projects dealing with u{\hyphen}LMS confirmed mutations and deletions in RB1, TP53, and PTEN. In addition, whole{\hyphen}exome sequencing of u{\hyphen}LMS has confirmed and demonstrated frequent alterations in TP53, RB1, α-thalassemia/mental retardation syndrome X-linked (ATRX), and mediator complex subunit 12 (MED12)...
April 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29657128/genomic-features-of-response-to-combination-immunotherapy-in-patients-with-advanced-non-small-cell-lung-cancer
#6
Matthew D Hellmann, Tavi Nathanson, Hira Rizvi, Benjamin C Creelan, Francisco Sanchez-Vega, Arun Ahuja, Ai Ni, Jacki B Novik, Levi M B Mangarin, Mohsen Abu-Akeel, Cailian Liu, Jennifer L Sauter, Natasha Rekhtman, Eliza Chang, Margaret K Callahan, Jamie E Chaft, Martin H Voss, Megan Tenet, Xue-Mei Li, Kelly Covello, Andrea Renninger, Patrik Vitazka, William J Geese, Hossein Borghaei, Charles M Rudin, Scott J Antonia, Charles Swanton, Jeff Hammerbacher, Taha Merghoub, Nicholas McGranahan, Alexandra Snyder, Jedd D Wolchok
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis...
April 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29623111/case-report-whole-exome-sequencing-of-circulating-cell-free-tumor-dna-in-a-follicular-thyroid-carcinoma-patient-with-lung-and-bone-metastases
#7
Jianlu Song, Zhili Yang
Metastatic follicular thyroid carcinoma (FTC), unresectable or resistance to radioactive iodine, is associated with poor survival. It is believed that this kind of FTC is driven by mutated genes. However, what kind of changes of genome and underlying mechanisms are elusive. The aim of this article is to understand whether there are somatic mutations in circulating cell-free tumor DNA (cfDNA) in a FTC patient with lung and bone metastases. A 55-year-old woman was diagnosed with FTC with bone and lung metastases...
January 2018: Journal of Circulating Biomarkers
https://www.readbyqxmd.com/read/29616327/whole-exome-sequencing-identifies-key-mutated-genes-in-t790m-wildtype-cmet-unamplified-lung-adenocarcinoma-with-acquired-resistance-to-first-generation-egfr-tyrosine-kinase-inhibitors
#8
Chenguang Li, Hailin Liu, Bin Zhang, Liqun Gong, Yanjun Su, Zhenfa Zhang, Changli Wang
PURPOSE: Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma harboring EGFR-activating mutations will inevitably acquire resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs). EGFR T790M mutation and cMET amplification are common mechanisms. Further study is needed to explore unknown genomic alterations contributing to drug resistance. METHODS: Tumor and blood samples from 69 stage IIIB-IV NSCLC patients defined as acquired resistance to first-generation EGFR TKIs (gefitinib, erlotinib or ecotinib) were collected...
April 3, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29514626/an-information-theoretic-approach-to-the-modeling-and-analysis-of-whole-genome-bisulfite-sequencing-data
#9
Garrett Jenkinson, Jordi Abante, Andrew P Feinberg, John Goutsias
BACKGROUND: DNA methylation is a stable form of epigenetic memory used by cells to control gene expression. Whole genome bisulfite sequencing (WGBS) has emerged as a gold-standard experimental technique for studying DNA methylation by producing high resolution genome-wide methylation profiles. Statistical modeling and analysis is employed to computationally extract and quantify information from these profiles in an effort to identify regions of the genome that demonstrate crucial or aberrant epigenetic behavior...
March 7, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29511884/podoplanin-positive-cancer-associated-fibroblast-recruitment-within-cancer-stroma-is-associated-with-a-higher-number-of-single-nucleotide-variants-in-cancer-cells-in-lung-adenocarcinoma
#10
Shoko Nakasone, Sachiyo Mimaki, Tomohiro Ichikawa, Keiju Aokage, Tomohiro Miyoshi, Masato Sugano, Motohiro Kojima, Satoshi Fujii, Takeshi Kuwata, Atsushi Ochiai, Masahiro Tsuboi, Koichi Goto, Katsuya Tsuchihara, Genichiro Ishii
PURPOSE: Podoplanin-positive cancer-associated fibroblasts (CAFs) play an essential role in tumor progression. However, it is still unclear whether specific genomic alterations of cancer cells are required to recruit podoplanin-positive CAFs. The aim of this study was to investigate the relationship between the mutation status of lung adenocarcinoma cells and the presence of podoplanin-positive CAFs. METHODS: Ninety-seven lung adenocarcinomas for which whole exome sequencing data were available were enrolled...
May 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29501208/-precision-medicine-a-major-step-forward-in-specific-situations-a-myth-in-refractory-cancers
#11
REVIEW
Nicolas Albin, Anne Mc Leer, Linda Sakhri
In recent years, high-throughput sequencing techniques have been developed for cancerology and many clinical trials are currently structured around biomarkers that can guide specific treatment choices. This approach is characteristic of precision medicine, which is actually a concept initiated several decades ago with, for example, retinoic acid in promyelocytic leukemia. This paper will review the different types of molecular alterations and « -omics » biological analyses, bioinformatics tools, coupled drug/biomarkers already validated, the ethical issues of whole genomic sequencing of an individual as part of an inclusion in a clinical trial and finally the first results of precision medicine trials...
April 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29494651/a-streamlined-workflow-for-single-cells-genome-wide-copy-number-profiling-by-low-pass-sequencing-of-lm-pcr-whole-genome-amplification-products
#12
Alberto Ferrarini, Claudio Forcato, Genny Buson, Paola Tononi, Valentina Del Monaco, Mario Terracciano, Chiara Bolognesi, Francesca Fontana, Gianni Medoro, Rui Neves, Birte Möhlendick, Karim Rihawi, Andrea Ardizzoni, Semini Sumanasuriya, Penny Flohr, Maryou Lambros, Johann de Bono, Nikolas H Stoecklein, Nicolò Manaresi
Chromosomal instability and associated chromosomal aberrations are hallmarks of cancer and play a critical role in disease progression and development of resistance to drugs. Single-cell genome analysis has gained interest in latest years as a source of biomarkers for targeted-therapy selection and drug resistance, and several methods have been developed to amplify the genomic DNA and to produce libraries suitable for Whole Genome Sequencing (WGS). However, most protocols require several enzymatic and cleanup steps, thus increasing the complexity and length of protocols, while robustness and speed are key factors for clinical applications...
2018: PloS One
https://www.readbyqxmd.com/read/29483136/genomic-and-functional-fidelity-of-small-cell-lung-cancer-patient-derived-xenografts
#13
Benjamin J Drapkin, Julie George, Camilla L Christensen, Mari Mino-Kenudson, Ruben Dries, Tilak Sundaresan, Sarah Phat, David T Myers, Jun Zhong, Peter Igo, Mehlika H Hazar-Rethinam, Joseph A Licausi, Maria Gomez-Caraballo, Marina Kem, Kandarp N Jani, Roxana Azimi, Nima Abedpour, Roopika Menon, Sotirios Lakis, Rebecca S Heist, Reinhard Büttner, Stefan Haas, Lecia V Sequist, Alice T Shaw, Kwok-Kin Wong, Aaron N Hata, Mehmet Toner, Shyamala Maheswaran, Daniel A Haber, Martin Peifer, Nicholas Dyson, Roman K Thomas, Anna F Farago
Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a 2-year timeframe, at 89% and 38% efficiency, respectively. Whole-exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs...
May 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29474635/genetic-mutations-associated-with-lung-cancer-metastasis-to-the-brain
#14
Hashim M Aljohani, Mohamed Aittaleb, John M Furgason, Peter Amaya, Ayham Deeb, Jeffery J Chalmers, El Mustapha Bahassi
Approximately 90% of all cancer deaths arise from the metastatic spread of primary tumours. Of all the processes involved in carcinogenesis, local invasion and the formation of metastases are clinically the most relevant, but they are the least well understood at the molecular level. As a barrier to metastasis, cells normally undergo an apoptotic process known as 'anoikis', in circulation. The recent technological advances in the isolation and characterisation of rare circulating tumour cells (CTCs) will allow a better understanding of anoikis resistance...
April 13, 2018: Mutagenesis
https://www.readbyqxmd.com/read/29459639/imaging-genotyping-of-functional-signaling-pathways-in-lung-squamous-cell-carcinoma-using-a-radiomics-approach
#15
So Hyeon Bak, Hyunjin Park, Ho Yun Lee, Youngwook Kim, Hyung-Lae Kim, Sin-Ho Jung, Hyeseung Kim, Jonghoon Kim, Keunchil Park
Imaging features can be useful for identifying distinct genomic differences and have predictive power for certain phenotypes attributed to genomic mutations. We aimed to identify predictive imaging biomarkers that underpin genomic alterations and clinical outcomes in lung squamous cell carcinoma (SQCC) using a radiomics approach. In 57 patients with lung SQCC who underwent preoperative computed tomography (CT) and whole-exome DNA sequencing, 63 quantitative imaging features were extracted from CT and 73 clinicoradiological features including imaging features were classified into 8 categories: clinical, global, histogram-based, lung cancer-specific, shape, local, regional, and emphysema...
February 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29436261/an-epigenomic-approach-to-identifying-differential-overlapping-and-cis-acting-lncrnas-in-cisplatin-resistant-cancer-cells
#16
Olga Vera, Carlos Rodriguez-Antolin, Javier de Castro, Florian A Karreth, Thomas A Sellers, Inmaculada Ibanez de Caceres
Long noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensitive/resistant non-small cell lung cancer and ovarian cancer cell lines. The epigenetic landscape of overlapping and cis-acting lncRNAs was determined by combining human microarray data on 30,586 lncRNAs and 20,109 protein coding mRNAs with whole-genome bisulfite sequencing...
April 2, 2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29413762/the-epithelial-sodium-channel-%C3%AE-enac-is-a-downstream-therapeutic-target-of-ascl1-in-pulmonary-neuroendocrine-tumors
#17
Min He, Shanshan Liu, Sachith Gallolu Kankanamalage, Mark D Borromeo, Luc Girard, Adi F Gazdar, John D Minna, Jane E Johnson, Melanie H Cobb
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma, designated as a recalcitrant cancer by the National Cancer Institute, in urgent need of new rational therapeutic targets. Previous studies have determined that the basic helix-loop-helix transcription factor achaete-scute homolog 1 (ASCL1) is essential for the survival and progression of a fraction of pulmonary neuroendocrine cancer cells, which include both SCLC and a subset of non-SCLC. Previously, to understand how ASCL1 initiates tumorigenesis in pulmonary neuroendocrine cancer and identify the transcriptional targets of ASCL1, whole-genome RNA-sequencing analysis combined with chromatin immunoprecipitation-sequencing was performed with a series of lung cancer cell lines...
April 2018: Translational Oncology
https://www.readbyqxmd.com/read/29413684/human-epidermal-receptor-family-inhibitors-in-patients-with-erbb3-mutated-cancers-entering-the-back-door
#18
Loic Verlingue, Antoine Hollebecque, Ludovic Lacroix, Sophie Postel-Vinay, Andrea Varga, Yolla El Dakdouki, Capucine Baldini, Rastilav Balheda, Anas Gazzah, Jean-Marie Michot, Aurélien Marabelle, Olivier Mir, Monica Arnedos, Etienne Rouleau, Eric Solary, Thierry De Baere, Eric Angevin, Jean-Pierre Armand, Stefan Michiels, Fabrice André, Eric Deutsch, Jean-Yves Scoazec, Jean-Charles Soria, Christophe Massard
INTRODUCTION: Therapeutic inhibition of the human epidermal receptor 3 (ERBB3, HER3) has been challenged by the low frequency of ERBB3 somatic alterations across cancer types. We have evaluated the clinical utility to use available inhibitors of the HER family in the context of ERBB3 mutations. PATIENTS AND METHODS: In this study, we have selected patients with somatic ERBB3 alterations detected in their tumours from the molecular screening programs running at our institution...
March 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29410677/development-of-a-method-to-implement-whole-genome-bisulfite-sequencing-of-cfdna-from-cancer-patients-and-a-mouse-tumor-model
#19
Elaine C Maggi, Silvia Gravina, Haiying Cheng, Bilal Piperdi, Ziqiang Yuan, Xiao Dong, Steven K Libutti, Jan Vijg, Cristina Montagna
The goal of this study was to develop a method for whole genome cell-free DNA (cfDNA) methylation analysis in humans and mice with the ultimate goal to facilitate the identification of tumor derived DNA methylation changes in the blood. Plasma or serum from patients with pancreatic neuroendocrine tumors or lung cancer, and plasma from a murine model of pancreatic adenocarcinoma was used to develop a protocol for cfDNA isolation, library preparation and whole-genome bisulfite sequencing of ultra low quantities of cfDNA, including tumor-specific DNA...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29374067/rnf6-promotes-colorectal-cancer-by-activating-the-wnt-%C3%AE-catenin-pathway-via-ubiquitination-of-tle3
#20
Lei Liu, Yanquan Zhang, Chi Chun Wong, Jingwan Zhang, Yujuan Dong, Xiangchun Li, Wei Kang, Francis K L Chan, Joseph J Y Sung, Jun Yu
Gene amplification is a hallmark of cancer and is frequently observed in colorectal cancer. Previous whole-genome sequencing of colorectal cancer clinical specimens identified amplification of Ring finger protein 6 (RNF6), a RING-domain E3 ubiquitin ligase. In this study, we showed that RNF6 is upregulated in 73.5% (147/200) of patients with colorectal cancer and was positively associated with RNF6 gene amplification. Furthermore, RNF6 expression and its gene amplification were independent prognostic factors for poor outcome of patients with colorectal cancer...
April 15, 2018: Cancer Research
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