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whole genome sequencing AND lung cancer

Hongdo Do, Daniel Cameron, Ramyar Molania, Bibhusal Thapa, Gareth Rivalland, Paul L Mitchell, Carmel Murone, Thomas John, Anthony Papenfuss, Alexander Dobrovic
Identifying circulating tumour DNA (ctDNA) for monitoring of cancer therapy is dependent on the development of readily designed, sensitive cancer-specific DNA markers. Genomic rearrangements that are present in the vast majority of cancers provide such markers.Tumour DNA isolated from two fresh-frozen lung tumours underwent whole genome sequencing. Genomic rearrangements were detected using a new computational algorithm, GRIDSS. Four genomic rearrangements from each tumour were chosen for further study using rearrangement-specific primers...
2016: Advances in Experimental Medicine and Biology
Fiona Taylor, James Bradford, Penella J Woll, Dawn Teare, Angela Cox
Molecular profiling using low coverage whole genome sequencing of cell free DNA (cfDNA) represents a non-targeted approach to identify multiple somatic copy number alterations (SCNA) across different lung cancer subtypes. We aim to establish that SCNA can be detected in cfDNA of lung cancer cases.Standard protocols were followed to process matched cfDNA, formalin-fixed paraffin embedded (FFPE) tumour and lymphocyte DNA. Copy number profiles for cfDNA or FFPE DNA were normalised to profiles from matched lymphocyte DNA with the software CNAnorm...
2016: Advances in Experimental Medicine and Biology
Xin Li, Yun Liu, Tal Salz, Kasper D Hansen, Andrew P Feinberg
DNA methylation at the 5-postion of cytosine (5mC) is an epigenetic modification that regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), providing an active mechanism for DNA demethylation, and may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in paired human liver and lung normal and cancer...
October 13, 2016: Genome Research
L Hua, W Y Zheng, H Xia, P Zhou
Comprehensive multi-omics data analyses have become an important means for understanding cancer incidence and progression largely driven by the availability of high-throughput sequencing technologies for genomes, proteomes, and transcriptomes. However, how tumor cells from the site of origin of the cancer begin to grow in other sites of the body is very poorly understood. In order to examine potential connections between different cancers and to gain an insight into the metastatic process, we conducted a multi-omics data analysis using data deposited in The Cancer Genome Atlas database...
August 19, 2016: Genetics and Molecular Research: GMR
David G McFadden, Katerina Politi, Arjun Bhutkar, Frances K Chen, Xiaoling Song, Mono Pirun, Philip M Santiago, Caroline Kim-Kiselak, James T Platt, Emily Lee, Emily Hodges, Adam P Rosebrock, Roderick T Bronson, Nicholas D Socci, Gregory J Hannon, Tyler Jacks, Harold Varmus
Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Kazuya Takamochi, Hiroko Ohmiya, Masayoshi Itoh, Kaoru Mogushi, Tsuyoshi Saito, Kieko Hara, Keiko Mitani, Yasushi Kogo, Yasunari Yamanaka, Jun Kawai, Yoshihide Hayashizaki, Shiaki Oh, Kenji Suzuki, Hideya Kawaji
BACKGROUND: Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed...
September 29, 2016: BMC Cancer
Hong Zheng, Wei Dai, Arthur Kwok Leung Cheung, Josephine Mun Yee Ko, Rebecca Kan, Bonnie Wing Yan Wong, Merrin Man Long Leong, Mingdan Deng, Tommy Chin Tung Kwok, Jimmy Yu-Wai Chan, Dora Lai-Wan Kwong, Anne Wing-Mui Lee, Wai Tong Ng, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Tung, Victor Ho-Fun Lee, Ka-On Lam, Chung Kong Kwan, Wing Sum Li, Stephen Yau, Kwok-Wah Chan, Maria Li Lung
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3 Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Le-Le Zhang, Mengyuan Kan, Man-Man Zhang, Sha-Sha Yu, Hui-Jun Xie, Zhao-Hui Gu, Hai-Ning Wang, Shuang-Xia Zhao, Guang-Biao Zhou, Huai-Dong Song, Cui-Xia Zheng
Intratumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) may account for resistance after a period of targeted therapies because drugs destroy only a portion of tumor cells. The recognition of ITH helps identify high-risk patients to make effective treatment decisions. However, ITH studies are confounded by interpatient heterogeneity in NSCLC and a large amount of passenger mutations. To address these issues, we recruited NSCLC patients carrying TP53 mutations and selected driver mutations within recurrently mutated genes in NSCLC...
September 20, 2016: International Journal of Cancer. Journal International du Cancer
Sang-Won Um, Je-Gun Joung, Hyun Lee, Hojoong Kim, Kyu-Tae Kim, Jinha Park, D Neil Hayes, Woong Yang Park
Tumor heterogeneity influences the clinical outcome of cancer patients, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six lung cancer patients using whole exome sequencing and RNA-seq. Although somatic single nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomical location of the tumors...
September 13, 2016: Cancer Research
Julie George, Motonobu Saito, Koji Tsuta, Reika Iwakawa, Kouya Shiraishi, Andreas Scheel, Shinsuke Uchida, Shun-Ichi Watanabe, Ryo Nishikawa, Masayuki Noguchi, Martin Peifer, Iver Petersen, Se Jin Jang, Reinhard Buttners, Curtis C Harris, Jun Yokota, Roman K Thomas, Takashi Kohno
BACKGROUND: Programmed death ligand-1 (PD-L1), encoded by the CD274 gene, is a target for immune checkpoint blockade; however, little is known about genomic CD274 alterations. A subset of small cell lung cancer (SCLC) exhibits increased copy number of chromosome 9p24, on which CD274 resides; however, most SCLCs show low expression of PD-L1. We therefore examined, whether CD274 is a target of recurrent genomic alterations. METHODS: We examined somatic copy number alterations in two patient cohorts by quantitative real-time PCR in 72 human SCLC cases (cohort 1), and SNP array analysis in 138 human SCLC cases (cohort 2)...
September 12, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Silvia Bonfiglio, Irene Vanni, Valeria Rossella, Anna Truini, Dejan Lazarevic, Maria Giovanna Dal Bello, Angela Alama, Marco Mora, Erika Rijavec, Carlo Genova, Davide Cittaro, Francesco Grossi, Simona Coco
BACKGROUND: Next Generation Sequencing (NGS) has become a valuable tool for molecular landscape characterization of cancer genomes, leading to a better understanding of tumor onset and progression, and opening new avenues in translational oncology. Formalin-fixed paraffin-embedded (FFPE) tissue is the method of choice for storage of clinical samples, however low quality of FFPE genomic DNA (gDNA) can limit its use for downstream applications. METHODS: To investigate the FFPE specimen suitability for NGS analysis and to establish the performance of two solution-based exome capture technologies, we compared the whole-exome sequencing (WES) data of gDNA extracted from 5 fresh frozen (FF) and 5 matched FFPE lung adenocarcinoma tissues using: SeqCap EZ Human Exome v...
2016: BMC Cancer
Chanida Vinayanuwattikun, Florence Le Calvez-Kelm, Behnoush Abedi-Ardekani, David Zaridze, Anush Mukeria, Catherine Voegele, Maxime Vallée, Dewajani Purnomosari, Nathalie Forey, Geoffroy Durand, Graham Byrnes, James Mckay, Paul Brennan, Ghislaine Scelo
To examine the diversity of somatic alterations and clonal evolution according to aggressiveness of disease, nineteen tumor-blood pairs of 'formerly bronchiolo-alveolar carcinoma (BAC)' which had been reclassified into preinvasive lesion (adenocarcinoma in situ; AIS), focal invasive lesion (minimally invasive adenocarcinoma; MIA), and invasive lesion (lepidic predominant adenocarcinoma; LPA and non-lepidic predominant adenocarcinoma; non-LPA) according to IASLC/ATS/ERS 2011 classification were explored by whole exome sequencing...
2016: Scientific Reports
Mathias Stiller, Antje Sucker, Klaus Griewank, Daniela Aust, Gustavo Bruno Baretton, Dirk Schadendorf, Susanne Horn
DNA derived from formalin-fixed and paraffin-embedded (FFPE) tissue has been a challenge to large-scale genomic sequencing, due to its low quality and quantities. Improved techniques enabling the genome-wide analysis of FFPE material would be of great value, both from a research and clinical perspective.Comparing a single-strand DNA library preparation method originally developed for ancient DNA to conventional protocols using double-stranded DNA derived from FFPE material we obtain on average 900-fold more library molecules and improved sequence complexity from as little as 5 ng input DNA...
July 24, 2016: Oncotarget
Andrea Garofalo, Lynette Sholl, Brendan Reardon, Amaro Taylor-Weiner, Ali Amin-Mansour, Diana Miao, David Liu, Nelly Oliver, Laura MacConaill, Matthew Ducar, Vanesa Rojas-Rudilla, Marios Giannakis, Arezou Ghazani, Stacy Gray, Pasi Janne, Judy Garber, Steve Joffe, Neal Lindeman, Nikhil Wagle, Levi A Garraway, Eliezer M Van Allen
BACKGROUND: The diversity of clinical tumor profiling approaches (small panels to whole exomes with matched or unmatched germline analysis) may engender uncertainty about their benefits and liabilities, particularly in light of reported germline false positives in tumor-only profiling and use of global mutational and/or neoantigen data. The goal of this study was to determine the impact of genomic analysis strategies on error rates and data interpretation across contexts and ancestries...
2016: Genome Medicine
Ronglai Shen, Venkatraman E Seshan
Allele-specific copy number analysis (ASCN) from next generation sequencing (NGS) data can greatly extend the utility of NGS beyond the identification of mutations to precisely annotate the genome for the detection of homozygous/heterozygous deletions, copy-neutral loss-of-heterozygosity (LOH), allele-specific gains/amplifications. In addition, as targeted gene panels are increasingly used in clinical sequencing studies for the detection of 'actionable' mutations and copy number alterations to guide treatment decisions, accurate, tumor purity-, ploidy- and clonal heterogeneity-adjusted integer copy number calls are greatly needed to more reliably interpret NGS-based cancer gene copy number data in the context of clinical sequencing...
September 19, 2016: Nucleic Acids Research
Masaru Katoh
Fibroblast growth factor (FGF)2, FGF4, FGF7 and FGF20 are representative paracrine FGFs binding to heparan-sulfate proteoglycan and fibroblast growth factor receptors (FGFRs), whereas FGF19, FGF21 and FGF23 are endocrine FGFs binding to Klotho and FGFRs. FGFR1 is relatively frequently amplified and overexpressed in breast and lung cancer, and FGFR2 in gastric cancer. BCR-FGFR1, CNTRL-FGFR1, CUX1-FGFR1, FGFR1OP-FGFR1, MYO18A-FGFR1 and ZMYM2-FGFR1 fusions in myeloproliferative neoplasms are non-receptor-type FGFR kinases, whereas FGFR1-TACC1, FGFR2-AFF3, FGFR2-BICC1, FGFR2-PPHLN1, FGFR3-BAIAP2L1 and FGFR3-TACC3 fusions in solid tumors are transmembrane-type FGFRs with C-terminal alterations...
July 2016: International Journal of Molecular Medicine
Leena Rivina, Michael J Davoren, Robert H Schiestl
Potential ionising radiation exposure scenarios are varied, but all bring risks beyond the simple issues of short-term survival. Whether accidentally exposed to a single, whole-body dose in an act of terrorism or purposefully exposed to fractionated doses as part of a therapeutic regimen, radiation exposure carries the consequence of elevated cancer risk. The long-term impact of both intentional and unintentional exposure could potentially be mitigated by treatments specifically developed to limit the mutations and precancerous replication that ensue in the wake of irradiation The development of such agents would undoubtedly require a substantial degree of in vitro testing, but in order to accurately recapitulate the complex process of radiation-induced carcinogenesis, well-understood animal models are necessary...
September 2016: Mutagenesis
Spencer D Martin, Scott D Brown, Darin A Wick, Julie S Nielsen, David R Kroeger, Kwame Twumasi-Boateng, Robert A Holt, Brad H Nelson
Due to advances in sequencing technology, somatically mutated cancer antigens, or neoantigens, are now readily identifiable and have become compelling targets for immunotherapy. In particular, neoantigen-targeted vaccines have shown promise in several pre-clinical and clinical studies. However, to date, neoantigen-targeted vaccine studies have involved tumors with exceptionally high mutation burdens. It remains unclear whether neoantigen-targeted vaccines will be broadly applicable to cancers with intermediate to low mutation burdens, such as ovarian cancer...
2016: PloS One
Monica K Akre, Gabriel J Starrett, Jelmar S Quist, Nuri A Temiz, Michael A Carpenter, Andrew N J Tutt, Anita Grigoriadis, Reuben S Harris
Molecular, cellular, and clinical studies have combined to demonstrate a contribution from the DNA cytosine deaminase APOBEC3B (A3B) to the overall mutation load in breast, head/neck, lung, bladder, cervical, ovarian, and other cancer types. However, the complete landscape of mutations attributable to this enzyme has yet to be determined in a controlled human cell system. We report a conditional and isogenic system for A3B induction, genomic DNA deamination, and mutagenesis. Human 293-derived cells were engineered to express doxycycline-inducible A3B-eGFP or eGFP constructs...
2016: PloS One
Ho Jang, Youngmi Hur, Hyunju Lee
DNA copy number alterations (CNAs) are the main genomic events that occur during the initiation and development of cancer. Distinguishing driver aberrant regions from passenger regions, which might contain candidate target genes for cancer therapies, is an important issue. Several methods for identifying cancer-driver genes from multiple cancer patients have been developed for single nucleotide polymorphism (SNP) arrays. However, for NGS data, methods for the SNP array cannot be directly applied because of different characteristics of NGS such as higher resolutions of data without predefined probes and incorrectly mapped reads to reference genomes...
2016: Scientific Reports
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