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https://www.readbyqxmd.com/read/28550027/exceptional-response-to-nivolumab-and-stereotactic-body-radiation-therapy-sbrt-in-neuroendocrine-cervical-carcinoma-with-high-tumor-mutational-burden-management-considerations-from-the-center-for-personalized-cancer-therapy-at-uc-san-diego-moores-cancer-center
#1
Andrew Sharabi, Sangwoo Shawn Kim, Shumei Kato, Philip D Sanders, Sandip Pravin Patel, Parag Sanghvi, Elizabeth Weihe, Razelle Kurzrock
Neuroendocrine carcinoma of the cervix is an ultra-rare malignancy with a poor prognosis and limited treatment options. Checkpoint blockade immunotherapy has rapidly developed into an emerging standard of care for several common disease types. Interestingly, in preclinical and retrospective clinical data, radiation therapy has been demonstrated to synergize with checkpoint inhibitors. Here we report a patient with metastatic, chemotherapy-refractory neuroendocrine carcinoma who presented with partial bowel obstruction due to a large tumor burden...
May 26, 2017: Oncologist
https://www.readbyqxmd.com/read/28549623/standardising-rna-profiling-based-biomarker-application-in-cancer-the-need-for-robust-control-of-technical-variables
#2
REVIEW
James P Stewart, Susan Richman, Tim Maughan, Mark Lawler, Philip D Dunne, Manuel Salto-Tellez
Histopathology-based staging of colorectal cancer (CRC) has utility in assessing the prognosis of patient subtypes, but as yet cannot accurately predict individual patient's treatment response. Transcriptomics approaches, using array based or next generation sequencing (NGS) platforms, of formalin fixed paraffin embedded tissue can be harnessed to develop multi-gene biomarkers for predicting both prognosis and treatment response, leading to stratification of treatment. While transcriptomics can shape future biomarker development, currently <1% of published biomarkers become clinically validated tests, often due to poor study design or lack of independent validation...
May 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28548125/next-generation-sequencing-based-molecular-characterization-of-primary-urinary-bladder-adenocarcinoma
#3
Somak Roy, Dinesh Pradhan, Wayne L Ernst, Stephanie Mercurio, Yana Najjar, Rahul Parikh, Anil V Parwani, Reetesh K Pai, Rajiv Dhir, Marina N Nikiforova
Primary bladder adenocarcinoma is a rare and aggressive tumor with poor clinical outcomes and no standard of care therapy. Molecular biology of this tumor is unknown due to the lack of comprehensive molecular profiling studies. The study aimed to identify genomic alterations of clinical and therapeutic significance using next-generation sequencing and compare genomic profile of primary bladder adenocarcinoma with that of high-grade urothelial carcinoma and colorectal adenocarcinoma. A cohort of 15 well-characterized primary bladder adenocarcinoma was subjected to targeted next-generation sequencing for the identification of mutations and copy-number changes in 51 cancer-related genes...
May 26, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28546527/effect-of-necrosis-on-the-mirna-mrna-regulatory-network-in-crt-mg-human-astroglioma-cells
#4
So-Hee Ahn, Jung-Hyuck Ahn, Dong-Ryeol Ryu, Jisoo Lee, Min-Sun Cho, Youn-Hee Choi
Purpose: Glioblastoma multiforme (GBM) is the most common adult primary intracranial tumor. The remarkable features of GBM include central necrosis. MicroRNAs (miRNAs) have been considered as diagnostic/prognostic biomarkers for many cancers, including glioblastoma. However, the effect of necrosis on the miRNA expression profile and predicted miRNA-mRNA regulatory information remain unclear. The purpose of this study is to examine the effect of necrotic cells on the modulation of miRNA and mRNA expression profiles and miRNA-mRNA network in CRT-MG cells...
May 22, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28545022/a-high-throughput-method-to-detect-rna-profiling-by-integration-of-rt-mlpa-with-next-generation-sequencing-technology
#5
Jing Wang, Xue Yang, Haofeng Chen, Xuewei Wang, Xiangyu Wang, Yi Fang, Zhenyu Jia, Jidong Gao
RNA in formalin-fixed and paraffin-embedded (FFPE) tissues provides large amount of information indicating disease stages, histological tumor types and grades, as well as clinical outcomes. However, Detection of RNA expression levels in formalin-fixed and paraffin-embedded samples is extremely difficult due to poor RNA quality. Here we developed a high-throughput method, Reverse Transcription-Multiple Ligation-dependent Probe Sequencing (RT-MLPSeq), to determine expression levels of multiple transcripts in FFPE samples...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28543693/somatic-driver-mutations-in-melanoma
#6
REVIEW
Bobby Y Reddy, David M Miller, Hensin Tsao
Melanoma has one of the highest somatic mutational burdens among solid malignancies. Although the rapid progress in genomic research has contributed immensely to our understanding of the pathogenesis of melanoma, the clinical significance of the vast array of genomic alterations discovered by next-generation sequencing is far from being fully characterized. Most mutations prevalent in melanoma are simply neutral "passengers," which accompany functionally significant "drivers" under transforming conditions. The delineation of driver mutations from passenger mutations is critical to the development of targeted therapies...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28542843/next-generation-sequencing-of-a-family-with-a-high-penetrance-of-monoclonal-gammopathies-for-the-identification-of-candidate-risk-alleles
#7
Niccolo Bolli, Matteo Barcella, Erika Salvi, Francesca D'Avila, Antonio Vendramin, Chiara De Philippis, Nikhil C Munshi, Herve Avet-Loiseau, Peter J Campbell, Alberto Mussetti, Cristiana Carniti, Francesco Maura, Cristina Barlassina, Paolo Corradini, Vittorio Montefusco
BACKGROUND: The authors describe a family with a high penetrance of plasma cell dyscrasias, suggesting inheritance of an autosomal dominant risk allele. METHODS: The authors performed whole-exome sequencing and reported on a combined approach aimed at the identification of causative variants and risk loci, using the wealth of data provided by this approach. RESULTS: The authors identified gene mutations and single-nucleotide polymorphisms of potential significance, and pinpointed a known risk locus for myeloma as a potential area of transmissible risk in the family...
May 23, 2017: Cancer
https://www.readbyqxmd.com/read/28541638/role-and-clinical-application-of-next-generation-sequencing-ngs-for-ovarian-cancer
#8
EDITORIAL
Myong Cheol Lim, Leslie M Randall
No abstract text is available yet for this article.
July 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28541631/germline-and-somatic-mutations-in-homologous-recombination-genes-among-chinese-ovarian-cancer-patients-detected-using-next-generation-sequencing
#9
Qianying Zhao, Jiaxin Yang, Lei Li, Dongyan Cao, Mei Yu, Keng Shen
OBJECTIVE: To define genetic profiling of homologous recombination (HR) deficiency in Chinese ovarian cancer patients. METHODS: we have applied next-generation sequencing to detect deleterious mutations through all exons in 31 core HR genes. Paired whole blood and frozen tumor samples from 50 Chinese women diagnosed with epithelial ovarian carcinomas were tested to identify both germline and somatic variants. RESULTS: Deleterious germline HR-mutations were identified in 36% of the ovarian cancer patients...
July 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28540249/liquid-biopsies-for-bladder-cancer
#10
EDITORIAL
Douglas G Ward, Richard T Bryan
The development of accurate urinary biomarkers for the non-invasive detection of urothelial bladder cancer (UBC) could transform patient pathways by reducing reliance on cystoscopy, and the identification of highly prognostic (or even predictive) biomarkers could better guide patient management. A number of approaches are being utilised to address these challenges in both urinary- and plasma-borne tumour DNA (tDNA), so-called "liquid biopsies". Next generation sequencing (NGS) and droplet digital PCR (ddPCR) allow detection of very low levels of such tDNA amongst a large excess of non-tumour DNA, the former permitting large mutation panels to be assessed and the latter potentially identifying ultrarare mutant alleles yet restricted for multiplexing...
April 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28537807/next-generation-sequencing-identifies-gene-mutations-that-are-predictive-of-malignancy-in-residual-needle-rinses-collected-from-fine-needle-aspirations-of-thyroid-nodules
#11
Maren Y Fuller, Dina Mody, April Hull, Kristi Pepper, Heather Hendrickson, Randall Olsen
CONTEXT: - Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant. OBJECTIVE: - To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material...
May 24, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28536309/development-and-validation-of-an-ultra-deep-next-generation-sequencing-assay-for-testing-of-plasma-cell-free-dna-from-patients-with-advanced-cancer
#12
Filip Janku, Shile Zhang, Jill Waters, Li Liu, Helen Huang, Vivek Subbiah, David S Hong, Daniel Karp, Siqing Fu, Xuyu Cai, Nishma M Ramzanali, Kiran Madwani, Goran Cabrilo, Debra D Andrews, Yue Zhao, Milind Javle, Scott Kopetz, Rajyalakshmi Luthra, Hyunsung J Kim, Sante Gnerre, Ravi Vijaya Satya, Han-Yu Chuang, Kristina M Kruglyak, Jonathan Toung, Chen Zhao, Richard Shen, John Heymach, Funda Meric-Bernstam, Gordon B Mills, Jian-Bing Fan, Neeraj S Salathia
Purpose: Tumor-derived cell-free DNA (cfDNA) in plasma can be used for molecular testing and provide an attractive alternative to tumor tissue. Commonly used PCR-based technologies can test for limited number of alterations at the time. Therefore, novel ultrasensitive technologies capable of testing for a broad spectrum of molecular alterations are needed to further personalized cancer therapy. <p>Experimental Design: We developed a highly sensitive ultra-deep next-generation sequencing (NGS) assay using reagents from TruSeq Nano library preparation and Nextera Rapid Capture target enrichment kits to generate plasma cfDNA sequencing libraries for mutational analysis in 61 cancer-related genes using common bioinformatics tools...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28536037/identification-of-molecular-targets-in-vulvar-cancers
#13
Marguerite L Palisoul, Mary M Mullen, Rebecca Feldman, Premal H Thaker
OBJECTIVES: To identify molecular alterations that contribute to vulvar cancer pathogenesis with the intent of identifying molecular targets for treatment. METHODS: After retrospective analysis of a database of molecularly-profiled gynecologic cancer patients, 149 vulvar cancer patients were included and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and gene amplification (C/FISH)...
May 20, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28535585/good-laboratory-standards-for-clinical-next-generation-sequencing-cancer-panel-tests
#14
REVIEW
Jihun Kim, Woong-Yang Park, Nayoung K D Kim, Se Jin Jang, Sung-Min Chun, Chang-Ohk Sung, Jene Choi, Young-Hyeh Ko, Yoon-La Choi, Hyo Sup Shim, Jae-Kyung Won
Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS...
May 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28534251/sequencing-of-alk-inhibitors-in-alk-non-small-cell-lung-cancer
#15
REVIEW
Shirish M Gadgeel
Major therapeutic advances have occurred over the last several years in the management of advanced ALK+ NSCLC patients. Crizotinib was the first agent approved for the management of ALK+ NSCLC patients after it demonstrated significantly greater clinical benefit compared to chemotherapy. Several next generation ALK inhibitors have demonstrated clinical benefit in patients with crizotinib refractory NSCLC patients including in the CNS. Based on available data, therapy with a next generation ALK inhibitor can be initiated following therapy with crizotinib without any assessment of the molecular mechanisms of resistance...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#16
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28533222/fractionated-radiation-therapy-stimulates-anti-tumor-immunity-mediated-by-both-resident-and-infiltrating-polyclonal-t-cell-populations-when-combined-with-pd1-blockade
#17
Simon J Dovedi, Eleanor J Cheadle, Amy Popple, Edmund Poon, Michelle Morrow, Ross Stewart, Erik Yusko, Catherine Sanders, Marissa Vignali, Ryan Emerson, Harlan Robins, Robert W Wilkinson, Jamie Honeychurch, Timothy Illidge
Purpose: Radiotherapy (RT) is a highly effective anti-cancer treatment forming part of the standard of care for the majority of patients, but local and distal disease recurrence remains a major cause of mortality. RT is known to enhance tumor immunogenicity; however, the contribution and mechanisms of RT induced immune responses are unknown. <p>Experimental Design: The impact of low-dose fractionated RT (5 x 2 Gy) alone and in combination with αPD-1 mAb on the tumor microenvironment was evaluated by flow cytometry and next-generation sequencing (NGS) of the T-cell receptor (TCR)-repertoire...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28532404/use-of-the-qiagen-genereader-ngs-system-for-detection-of-kras-mutations-validated-by-the-qiagen-therascreen-pcr-kit-and-alternative-ngs-platform
#18
Agus Darwanto, Anne-Mette Hein, Sascha Strauss, Yi Kong, Andrew Sheridan, Dan Richards, Eric Lader, Monika Ngowe, Timothy Pelletier, Danielle Adams, Austin Ricker, Nishit Patel, Andreas Kühne, Simon Hughes, Dan Shiffman, Dirk Zimmermann, Kai Te Kaat, Thomas Rothmann
BACKGROUND: The detection of somatic mutations in primary tumors is critical for the understanding of cancer evolution and targeting therapy. Multiple technologies have been developed to enable the detection of such mutations. Next generation sequencing (NGS) is a new platform that is gradually becoming the technology of choice for genotyping cancer samples, owing to its ability to simultaneously interrogate many genomic loci at massively high efficiency and increasingly lower cost. However, multiple barriers still exist for its broader adoption in clinical research practice, such as fragmented workflow and complex bioinformatics analysis and interpretation...
May 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28531552/the-role-of-next-generation-sequencing-in-infection-prevention-in-human-parainfluenza-virus-3-infections-in-immunocompromised-patients
#19
Atul Kothari, Mary J Burgess, Juan Carlos Rico Crescencio, Joshua L Kennedy, Jesse L Denson, Kurt C Schwalm, Ashley N Stoner, John C Kincaid, Faith E Davies, Darrell L Dinwiddie
BACKGROUND: Respiratory viral infections are a significant problem in patients with hematologic malignancies. We report a cluster of HPIV 3 infections in our myeloma patients, and describe the utility of next generation sequencing (NGS) to identify transmission linkages which can assist in infection prevention. OBJECTIVES: To evaluate the utility of NGS to track respiratory viral infection outbreaks and delineate between community acquired and nosocomial infections in our cancer units...
May 12, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28531253/gender-related-prognostic-value-and-genomic-pattern-of-intra-tumor-heterogeneity-ith-in-colorectal-cancer
#20
Jieyun Zhang, Shican Yan, Xiyu Liu, Lu Gan, Zhenhua Wu, Yiwei Gong, Mingzhu Huang, Xiaowei Zhang, Weijian Guo
Intra-tumor heterogeneity (ITH) is crucial in tumorigenesis and resistance to target therapy. Here, we used mutant-allele tumor heterogeneity (MATH) to measure ITH based on next-generation sequencing data and high MATH was proven as an independent risk prognostic factor in male CRC patients in both a training set of 284 colorectal cancer (CRC) patients with from The Cancer Genome Atlas (TCGA) and a validating set of 187 CRC patients from International Cancer Genome Consortium (ICGC). Further, the genomic pattern according to MATH demonstrated that mutation rates of TP53, IRF5 and KRAS were independently associated with MATH, and the latter two were only significant in male patients...
May 20, 2017: Carcinogenesis
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