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Next generation sequencing AND lung cancer

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https://www.readbyqxmd.com/read/27900322/patterns-of-transposable-element-expression-and-insertion-in-cancer
#1
Evan A Clayton, Lu Wang, Lavanya Rishishwar, Jianrong Wang, John F McDonald, I King Jordan
Human transposable element (TE) activity in somatic tissues causes mutations that can contribute to tumorigenesis. Indeed, TE insertion mutations have been implicated in the etiology of a number of different cancer types. Nevertheless, the full extent of somatic TE activity, along with its relationship to tumorigenesis, have yet to be fully explored. Recent developments in bioinformatics software make it possible to analyze TE expression levels and TE insertional activity directly from transcriptome (RNA-seq) and whole genome (DNA-seq) next-generation sequence data...
2016: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/27899957/next-generation-sequencing-in-nsclc-and-melanoma-patients-a-cost-and-budget-impact-analysis
#2
Rosa A van Amerongen, Valesca P Retèl, Veerle Mh Coupé, Petra M Nederlof, Maartje J Vogel, Wim H van Harten
Next-generation sequencing (NGS) has reached the molecular diagnostic laboratories. Although the NGS technology aims to improve the effectiveness of therapies by selecting the most promising therapy, concerns are that NGS testing is expensive and that the 'benefits' are not yet in relation to these costs. In this study, we give an estimation of the costs and an institutional and national budget impact of various types of NGS tests in non-small-cell lung cancer (NSCLC) and melanoma patients within The Netherlands...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27899772/-lung-cancer
#3
Kazushi Yoshida, Takashi Kono
Personalized lung cancer therapy has progressed by targeting several oncogenic aberrations that drive lung carcinogenesis. Recent advances in gene analysis technologies, including next-generation sequencing that yields large amounts of genomic data, have greatly contributed to this progress. In addition, immune checkpoint blockade therapy has become available in Japan, and extensive searches for biomarkers predictive of therapeutic response have been carried out. "Clinical sequencing" which analyzes aberrations in a set of therapy-related genes in patient cancer specimens, has been actively conducted in Japan and other countries...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27889782/molecular-pathology-a-requirement-for-precision-medicine-in-cancer
#4
Manfred Dietel
The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27875625/clinical-and-genetic-determinants-of-ovarian-metastases-from-colorectal-cancer
#5
Karuna Ganesh, Ronak H Shah, Efsevia Vakiani, Garrett M Nash, Hugh P Skottowe, Rona Yaeger, Andrea Cercek, Anne Lincoln, Christina Tran, Neil H Segal, Diane L Reidy, Anna Varghese, Andrew S Epstein, Yukio Sonoda, Dennis Chi, Jose Guillem, Larissa Temple, Philip Paty, Jaclyn Hechtman, Jinru Shia, Martin Weiser, Julio Garcia Aguilar, Nancy Kemeny, Michael F Berger, Leonard Saltz, Zsofia K Stadler
BACKGROUND: Ovarian metastases from colorectal cancer (OM-CRC) often are unresponsive to chemotherapy and are associated with poor survival. To the authors' knowledge, the clinicopathologic and genomic predictors of OM-CRC are poorly characterized and optimal clinical management remains unclear. METHODS: Women with a histopathological diagnosis of OM-CRC who were treated at Memorial Sloan Kettering Cancer Center from 1999 to 2015 were identified. Next-generation somatic mutation profiling (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]) was performed on 38 OM-CRC cases, including 21 matched tumor pairs/trios...
November 22, 2016: Cancer
https://www.readbyqxmd.com/read/27866095/continuing-egfr-inhibition-beyond-progression-in-advanced-non-small-cell-lung-cancer
#6
REVIEW
Timothy A Yap, Aislinn Macklin-Doherty, Sanjay Popat
The majority of patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) respond to first-line EGFR tyrosine kinase inhibitors (TKIs), but nearly all inevitably acquire resistance and develop disease progression. Conventional practice would be to switch treatments to second-line therapy. However, continuing TKIs beyond progression is becoming increasingly commonplace in patients with indolent, small volume asymptomatic growth, who may potentially continue to derive ongoing clinical benefit and to avoid a 'withdrawal tumour flare'...
November 17, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27865871/clinical-impact-of-hybrid-capture-based-next-generation-sequencing-on-changes-in-treatment-decisions-in-lung-cancer
#7
Anna Belilovski Rozenblum, Maya Ilouze, Elizabeth Dudnik, Addie Dvir, Lior Soussan-Gutman, Smadar Geva, Nir Peled
INTRODUCTION: Targeted therapy significantly prolongs survival in lung adenocarcinoma. Current diagnostic guidelines include only EGFR and ALK testing. Next-generation sequencing (NGS) reveals more actionable genomic alterations (GAs) than stan dard diagnostic methods. Data on the influence of hybrid capture-based (HC-based) NGS on treatment are limited, and we investigated its impact on treatment decisions/clinical outcomes. METHODS: This retrospective study included patients with advanced lung cancer on whom HC-based NGS was performed between 11/2011-10/2015...
November 9, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27865624/w-alk-into-the-next-stage
#8
REVIEW
Gouji Toyokawa, Takashi Seto, Mitsuhiro Takenoyama, Yukito Ichinose
In 2007, the rearrangement of anaplastic lymphoma kinase (ALK) was identified to be associated with the pathogenesis of a subset of patients with non-small-cell lung cancer (NSCLC). Surprisingly, approximately 4 years after the discovery of ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi), crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and Drug Administration. Subsequently, next-generation ALKis, such as alectinib and ceritinib, have been developed, and some of them have been applied in the clinical setting...
October 26, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27863497/next-generation-sequencing-facilitates-detection-of-the-classic-e13-a20-eml4-alk-fusion-in-an-alk-fish-ihc-inconclusive-biopsy-of-a-stage-iv-lung-cancer-patient-a-case-report
#9
Anna-Lena Volckmar, Volker Endris, Farastuk Bozorgmehr, Clemens Lier, Carlota Porcel, Martina Kirchner, Jonas Leichsenring, Roland Penzel, Michael Thomas, Peter Schirmacher, Arne Warth, Albrecht Stenzinger
BACKGROUND: Inhibition of the oncogenic fusion-gene EML4-ALK is a current first-line approach for patients with stage IV non-small cell lung cancer. While FISH was established as the gold standard for identifying these patients, there is accumulating evidence that other methods of detection, i.e., immunohistochemistry and next-generation sequencing (NGS), exist that may be equally successful. However, the concordance of these methods is under investigation. CASE PRESENTATION: Adding to the current literature, we here report a 56 year old female never-smoker with stage IV lung adenocarcinoma whose biopsy was IHC and FISH inconclusive but positive in NGS...
November 18, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27844240/identification-of-a-rare-germline-nbn-gene-mutation-by-whole-exome-sequencing-in-a-lung-cancer-survivor-from-a-large-family-with-various-types-of-cancer
#10
Makia J Marafie, Mohammed Dashti, Fahd Al-Mulla
Nijmegen breakage syndrome is an autosomal recessive disorder caused by biallelic mutation in NBN gene. It is characterized by microcephaly, growth retardation, immuno-deficiency and cancer predisposition. The monoallelic carriers of NBN gene are also reported to be at increased risk of developing various types of malignancy. We have investigated an individual with lung cancer from an extended family segregating different types of hereditary cancer over several generations, including lung, breast, ovarian, colon, prostate and renal cancers...
November 14, 2016: Familial Cancer
https://www.readbyqxmd.com/read/27826531/next-generation-sequencing-techniques-in-liquid-biopsy-focus-on-non-small-cell-lung-cancer-patients
#11
REVIEW
Umberto Malapelle, Pasquale Pisapia, Danilo Rocco, Riccardo Smeraglio, Maria di Spirito, Claudio Bellevicine, Giancarlo Troncone
The advent of genomic based personalized medicine has led to multiple advances in the molecular characterization of many tumor types, such as non-small cell lung cancer (NSCLC). NSCLC is diagnosed in most cases on small tissue samples that may be not always sufficient for EGFR mutational assessment to select patients for first and second generations' tyrosine kinase inhibitors (TKIs) therapy. In patients without tissue availability at presentation, the analysis of cell free DNA (cfDNA) derived from liquid biopsy samples, in particular from plasma, represent an established alternative to provide EGFR mutational testing for treatment decision making...
October 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/27825109/her2-mutations-in-chinese-patients-with-non-small-cell-lung-cancer
#12
Zhengbo Song, Xinmin Yu, Zhiyong Shi, Jun Zhao, Yiping Zhang
BACKGROUND: ERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear. PATIENTS AND METHODS: Eight hundred and fifty-nine patients with pathologically confirmed NSCLC were screened for HER2 mutations using Sanger sequencing. Next-generation sequencing (NGS) was performed in positive cases. HER2 amplification was detected with FISH...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27794403/clinicopathologic-characteristics-genetic-variability-and-therapeutic-options-of-ret-rearrangements-patients-in-lung-adenocarcinoma
#13
Zhengbo Song, Xinmin Yu, Yiping Zhang
BACKGROUND: RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients. PATIENTS AND METHODS: For 615 patients with lung adenocarcinoma, RET status was detected by reverse transcription-polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) and FISH were performed in positive cases...
November 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27794398/case-report-durable-response-to-afatinib-in-a-patient-with-lung-cancer-harboring-two-uncommon-mutations-of-egfr-and-a-kras-mutation
#14
Junko Tanizaki, Eri Banno, Yosuke Togashi, Hidetoshi Hayashi, Kazuko Sakai, Masayuki Takeda, Hiroyasu Kaneda, Kazuto Nishio, Kazuhiko Nakagawa
Comprehensive genomic profiling for non-small cell lung cancer (NSCLC) is likely to identify more patients with rare genetic alterations including uncommon epidermal growth factor receptor gene (EGFR) mutations. It remains unclear how such patients should be treated, however. We here report a case of NSCLC positive for two uncommon mutations of EGFR and a KRAS mutation, including its treatment with the second-generation EGFR tyrosine kinase inhibitor (TKI) afatinib. Tumor specimen obtained by a NSCLC patient with no smoking history was analyzed by next-generation sequencing...
November 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27776519/novel-algorithmic-approach-predicts-tumor-mutation-load-and-correlates-with-immunotherapy-clinical-outcomes-using-a-defined-gene-mutation-set
#15
Jason Roszik, Lauren E Haydu, Kenneth R Hess, Junna Oba, Aron Y Joon, Alan E Siroy, Tatiana V Karpinets, Francesco C Stingo, Veera Baladandayuthapani, Michael T Tetzlaff, Jennifer A Wargo, Ken Chen, Marie-Andrée Forget, Cara L Haymaker, Jie Qing Chen, Funda Meric-Bernstam, Agda K Eterovic, Kenna R Shaw, Gordon B Mills, Jeffrey E Gershenwald, Laszlo G Radvanyi, Patrick Hwu, P Andrew Futreal, Don L Gibbons, Alexander J Lazar, Chantale Bernatchez, Michael A Davies, Scott E Woodman
BACKGROUND: While clinical outcomes following immunotherapy have shown an association with tumor mutation load using whole exome sequencing (WES), its clinical applicability is currently limited by cost and bioinformatics requirements. METHODS: We developed a method to accurately derive the predicted total mutation load (PTML) within individual tumors from a small set of genes that can be used in clinical next generation sequencing (NGS) panels. PTML was derived from the actual total mutation load (ATML) of 575 distinct melanoma and lung cancer samples and validated using independent melanoma (n = 312) and lung cancer (n = 217) cohorts...
October 25, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27774772/touch-imprint-cytology-with-massively-parallel-sequencing-tic-seq-a-simple-and-rapid-method-to-snapshot-genetic-alterations-in-tumors
#16
Kenji Amemiya, Yosuke Hirotsu, Taichiro Goto, Hiroshi Nakagomi, Hitoshi Mochizuki, Toshio Oyama, Masao Omata
Identifying genetic alterations in tumors is critical for molecular targeting of therapy. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissue is usually employed for genetic analysis. However, DNA extracted from FFPE tissue is often not suitable for analysis because of its low levels and poor quality. Additionally, FFPE sample preparation is time-consuming. To provide early treatment for cancer patients, a more rapid and robust method is required for precision medicine. We present a simple method for genetic analysis, called touch imprint cytology combined with massively paralleled sequencing (touch imprint cytology [TIC]-seq), to detect somatic mutations in tumors...
October 24, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27769776/immunotherapy-of-lung-malignancies-from-gene-sequencing-to-novel-therapies
#17
J Chee, B W S R Robinson, R A Holt, J Creaney
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Anti-tumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-PD1/anti-PDL1 antibodies causes tumor regression in around 25% of lung cancer patients. In another approach, the immune system is forced or accelerated to attack the tumour, via augmentation of the anti-tumour response against mutations carried by each lung tumour...
October 18, 2016: Chest
https://www.readbyqxmd.com/read/27763790/improving-adequacy-of-small-biopsy-and-fine-needle-aspiration-specimens-for-molecular-testing-by-next-generation-sequencing-in-patients-with-lung-cancer-a-quality-improvement-study-at-dartmouth-hitchcock-medical-center
#18
Vijayalakshmi Padmanabhan, Heather B Steinmetz, Elizabeth J Rizzo, Amber J Erskine, Tamara L Fairbank, Francine B de Abreu, Gregory J Tsongalis, Laura J Tafe
CONTEXT: -At our medical center, cytopathologists perform rapid on-site evaluation for specimen adequacy of fine-needle aspiration and touch imprint of needle core biopsy lung cancer samples. Two years ago the molecular diagnostics laboratory at our institution changed to next-generation sequencing using the Ion Torrent PGM and the 50-gene AmpliSeq Cancer Hotspot Panel v2 for analyzing mutations in a 50-gene cancer hot spot panel. This was associated with in a dramatic fall in adequacy rate (68%)...
October 20, 2016: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/27756406/spatio-temporal-mutation-profiles-of-case-matched-colorectal-carcinomas-and-their-metastases-reveal-unique-de-novo-mutations-in-metachronous-lung-metastases-by-targeted-next-generation-sequencing
#19
Valentina Kovaleva, Anna-Lena Geissler, Lisa Lutz, Ralph Fritsch, Frank Makowiec, Sebastian Wiesemann, Ulrich T Hopt, Bernward Passlick, Martin Werner, Silke Lassmann
BACKGROUND: Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool for decision on EGFR-targeted therapy. Here, we investigated mutation profiles of case-matched tissue specimens throughout the disease course of CRC, to further specify RAS-status dynamics and to identify de novo mutations associated with distant metastases. METHODS: Case-matched formalin-fixed and paraffin-embedded (FFPE) resection specimens (n = 70; primary tumours, synchronous and/or metachronous liver and/or lung metastases) of 14 CRC cases were subjected to microdissection of normal colonic epithelial, primary and metastatic tumour cells, their DNA extraction and an adapted library protocol for limited DNA using the 48 gene TruSeq Amplicon Cancer Panel(TM), MiSeq sequencing and data analyses (Illumina)...
October 18, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27750395/synonymous-egfr-variant-p-q787q-is-neither-prognostic-nor-predictive-in-patients-with-lung-adenocarcinoma
#20
Jonas Leichsenring, Anna-Lena Volckmar, Nikolaus Magios, Cristiano Manuel Morais de Oliveira, Roland Penzel, Regine Brandt, Martina Kirchner, Farastuk Bozorgmehr, Michael Thomas, Peter Schirmacher, Arne Warth, Volker Endris, Albrecht Stenzinger
Patients with non-small cell lung cancer (NSCLC) harboring activating mutations in the Epidermal Growth Factor Receptor (EGFR) benefit from targeted therapies. A synonymous polymorphism (rs1050171, p.Q787Q) was shown to be associated with improved overall survival (OS) in colorectal cancer patients. As data in NSCLC are limited, we retrospectively analyzed associations of p.Q787Q with clinicopathological parameters including clinical response and outcome in patients with lung adenocarcinoma (ADC) who received tyrosine kinase inhibitor (TKI) therapy...
October 17, 2016: Genes, Chromosomes & Cancer
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