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Next generation sequencing AND cancer

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https://www.readbyqxmd.com/read/28745580/pharmacogenomic-considerations-in-the-treatment-of-muscle-invasive-bladder-cancer
#1
Tahlita Cm Zuiverloon, Dan Theodorescu
Recent advances in next-generation sequencing techniques have greatly improved our understanding of the genomic alterations in bladder cancer. Cisplatin-based chemotherapy provides a viable treatment option in the neoadjuvant, adjuvant and metastatic setting in a selected group of patients, but chemoresistance is a major problem. The underlying mechanisms of treatment resistance are poorly understood and elucidating these pathways will subsequently lead to improved patient selection, less unnecessary drug-related toxicity, improved patient outcome and decreased healthcare costs...
July 26, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28745433/transcriptome-analysis-in-primary-colorectal-cancer-tissues-from-patients-with-and-without-liver-metastases-using-next-generation-sequencing
#2
Sen Wang, Chuan Zhang, Zhiyuan Zhang, Wenwei Qian, Ye Sun, Bing Ji, Yue Zhang, Chunyan Zhu, Dongjian Ji, Qingyuan Wang, Yueming Sun
Colorectal cancer (CRC) is the third most common cancer worldwide and liver metastases are the leading cause of death in patients with CRC. In this study, we performed next-generation sequencing profiling on primary colorectal tumor tissues obtained from three CRC patients with liver metastases and three CRC patients without liver metastases to identify differentially expressed genes (DEGs) that might be responsible for the metastases process. After filtering 2690 DEGs, comprising 996 upregulated and 1694 downregulated RNAs, 22 upregulated and 73 downregulated DEGs were identified...
July 26, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28743163/alk-and-ros1-testing-on-lung-cancer-cytologic-samples-perspectives
#3
REVIEW
Pasquale Pisapia, Maria D Lozano, Elena Vigliar, Claudio Bellevicine, Francesco Pepe, Umberto Malapelle, Giancarlo Troncone
Cytologic sampling is the mainstay of diagnosing advanced lung cancer. Moreover, to select patients for personalized first-line or second-line treatment, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements are tested on cytologic preparations. Commercially available fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC) assays have primarily been used for the identification of cells harboring ALK or ROS1 gene fusions on histologic rather than cytologic preparations...
July 25, 2017: Cancer
https://www.readbyqxmd.com/read/28740454/genetic-counselling-brca1-2-status-and-clinico-pathologic-characteristics-of-patients-with-ovarian-cancer-before-50-years-of-age
#4
Mirjam Cvelbar, Marko Hocevar, Srdjan Novakovic, Vida Stegel, Andraz Perhavec, Mateja Krajc
BACKGROUND: In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics...
June 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/28736761/phase-ii-study-of-dovitinib-in-patients-progressing-on-anti-vascular-endothelial-growth-factor-therapy
#5
Thomas J Semrad, Edward J Kim, Michael S Tanaka, Jacob Sands, Chris Roberts, Rebekah A Burich, Yu Li, David R Gandara, Primo Lara, Philip C Mack
BACKGROUND: Prior work identified the fibroblast growth factor (FGF) pathway as a mediator of resistance to anti-vascular endothelial growth factor (VEGF) therapy. We tested dovitinib, an inhibitor of both FGF and VEGF receptors, in patients progressing on anti-VEGF treatment. METHODS: Patients with measurable advanced colorectal or non-small cell lung cancer with progression despite anti-VEGF treatment within 56 days, good performance status and adequate organ function were eligible...
2017: Cancer Treat Res Commun
https://www.readbyqxmd.com/read/28736630/current-biologics-for-treatment-of-biliary-tract-cancers
#6
REVIEW
Diana Y Zhao, Kian-Huat Lim
Biliary tract cancers (BTC) is a group of malignancies that arise from the epithelial cells of the biliary tree. These cancers are typically classified by anatomic site of origin: intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC). To date, complete surgical resection remains the mainstay of treatment especially for earlier stage disease. Unfortunately, most patients present with advanced or metastatic disease, when systemic chemotherapy is the only treatment option...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736627/personalized-and-precision-medicine-integrating-genomics-into-treatment-decisions-in-gastrointestinal-malignancies
#7
REVIEW
Trang H Au, Kai Wang, David Stenehjem, Ignacio Garrido-Laguna
The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC)...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736138/how-viral-genetic-variants-and-genotypes-influence-disease-and-treatment-outcome-of-chronic-hepatitis-b-time-for-an-individualized-approach
#8
REVIEW
Neil Rajoriya, Christophe Combet, Fabien Zoulim, Harry L A Janssen
Chronic hepatitis B virus (HBV) infection remains a global problem. Several HBV (sub)genotypes exist with different biology and geographical preponderances. While the future aim of HBV treatment remains virus eradication, current strategies of treatment aim to suppress the virus and prevent the progression of liver disease. Current strategies also involve identification of patients for treatment - those at risk of progressive liver disease. Identification of HBV genotype, HBV mutants and other predictive factors allow for tailored treatments, and also risk-surveillance pathways such as for hepatocellular cancer screening...
July 20, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28735488/bioinformatics-data-analysis-of-next-generation-sequencing-data-from-heterogeneous-tumor-samples
#9
Sean R Landman, Tae Hyun Hwang
Tumor heterogeneity is a major challenge when it comes to treating cancer and also complicates research aimed at determining genetic sources for tumorigenesis. Leveraging high-throughput sequencing technology has been an effective approach for advancing our understanding of genetic diseases, and this type of data can also be used to better understand and make inferences about tumor heterogeneity. Here we describe the basics of genomics data analysis, as well as analysis pipelines for investigating tumor heterogeneity with next-generation sequencing data...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28734945/the-epigenomic-revolution-in-breast-cancer-from-single-gene-to-genome-wide-next-generation-approaches
#10
REVIEW
Veronica Davalos, Anna Martinez-Cardus, Manel Esteller
From the first identification of aberrant DNA methylation in primary human tumors more than three decades ago, exponential progress in cancer epigenetics research has been made. For many years, cancer epigenetics studies relied on identification of DNA methylation and histone modifications at specific genes. These studies laid the foundation for the field and revealed the epigenetic alterations as hallmark of cancer, as well as the crucial role of epigenetic mechanisms in tumorigenesis. The introduction of next-generation sequencing and array-based technologies for analyzing epigenetic states has accelerated our understanding about cancer and nowadays have become potent tools in our fight against the disease...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28734944/triple-negative-breast-cancer-next-generation-sequencing-for-target-identification
#11
REVIEW
Jonathan D Marotti, Francine B de Abreu, Wendy A Wells, Gregory J Tsongalis
Our ability to now study disease at the most fundamental molecular level has led to a reclassification of human cancers into numerous subtypes that vary in disease progression and response to therapy. Like most solid tumors, breast cancer is a heterogeneous disease with considerable variation in histological and biological features. Triple negative breast cancer (TNBC) is a subtype of breast cancer in which estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28734796/clonal-composition-of-human-ovarian-cancer-based-on-copy-number-analysis-reveals-a-reciprocal-relation-with-oncogenic-mutation-status
#12
Kazuko Sakai, Masayo Ukita, Jeanette Schmidt, Longyang Wu, Marco De Velasco, Alan Roter, Luis Jevons, Kazuto Nishio, Masaki Mandai
Intratumoral heterogeneity of cancer cells remains largely unexplored. Here we investigated the composition of ovarian cancer and its biological relevance. A whole-genome single nucleotide polymorphism array was applied to detect the clonal composition of 24 formalin-fixed, paraffin-embedded samples of human ovarian cancer. Genome-wide segmentation data consisting of the log2 ratio (log2R) and B allele frequency (BAF) were used to calculate an estimate of the clonal composition number (CC number) for each tumor...
July 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28733441/molecular-screening-for-cancer-treatment-optimization-moscato-01-in-pediatric-patients-a-single-institutional-prospective-molecular-stratification-trial
#13
Anne Catherine Harttrampf, Ludovic Lacroix, Marc Deloger, Frederic Deschamps, Stéphanie Puget, Nathalie Auger, Philippe Vielh, Pascale Varlet, Zsofia Balogh, Samuel Abbou, Adrien Allorant, Dominique Valteau-Couanet, Sabine Sarnacki, Louise Galmiche, Guillaume Meurice, Véronique Minard-Colin, Jacques Grill, Laurence Brugières, Christelle Dufour, Nathalie Gaspar, Stefan Michiels, Gilles Vassal, Jean-Charles Soria, Birgit Geoerger
This single institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients in order to select a targeted therapy.<br /><br />Experimental Design: Following treatment failure patients with signed consent and aged above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site.  These newly acquired samples were analyzed by comparative genomic hybridization array, next generation sequencing for 75 target genes, whole exome and RNA sequencing...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28732364/a-novel-heterozygous-germline-deletion-in-msh2-gene-in-a-five-generation-chinese-family-with-lynch-syndrome
#14
Bin Wu, Wuyang Ji, Shengran Liang, Chao Ling, Yan You, Lai Xu, Min-Er Zhong, Yi Xiao, Hui-Zhong Qiu, Jun-Yang Lu, Santasree Banerjee
Lynch syndrome (LS) is one of the most common familial forms of colorectal cancer predisposing syndrome with an autosomal dominant mode of inheritance. LS is caused by the germline mutations in DNA mismatch repair (MMR) genes including MSH2, MLH1, MSH6and PMS2. Clinically, LS is characterized by high incidence of early-onset colorectal cancer as well as endometrial, small intestinal and urinary tract cancers, usually occur in the third to fourth decade of the life. Here we describe a five generation Chinese family with LS clinically diagnosed according to the Amsterdam II criteria...
July 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732357/profiling-cancer-related-gene-mutations-in-oral-squamous-cell-carcinoma-from-japanese-patients-by-targeted-amplicon-sequencing
#15
Takafumi Nakagaki, Miyuki Tamura, Kenta Kobashi, Ryota Koyama, Hisayo Fukushima, Tomoko Ohashi, Masashi Idogawa, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino, Yasushi Sasaki
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732215/a-method-for-next-generation-sequencing-of-paired-diagnostic-and-remission-samples-to-detect-mitochondrial-dna-mutations-associated-with-leukemia
#16
Ilaria S Pagani, Chung H Kok, Verity A Saunders, Mark B Van der Hoek, Susan L Heatley, Anthony P Schwarer, Christopher N Hahn, Timothy P Hughes, Deborah L White, David M Ross
Somatic mitochondrial DNA (mtDNA) mutations have been identified in many human cancers, including leukemia. To identify somatic mutations, it is necessary to have a control tissue from the same individual for comparison. When patients with leukemia achieve remission, the remission peripheral blood may be a suitable and easily accessible control tissue, but this approach has not previously been applied to the study of mtDNA mutations. We have developed and validated a next-generation sequencing approach for the identification of leukemia-associated mtDNA mutations in 26 chronic myeloid leukemia patients at diagnosis using either nonhematopoietic or remission blood samples as the control...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28732214/crispr-cas9-technology-based-xenograft-tumors-as-candidate-reference-materials-for-multiple-eml4-alk-rearrangements-testing
#17
Rongxue Peng, Rui Zhang, Guigao Lin, Xin Yang, Ziyang Li, Kuo Zhang, Jiawei Zhang, Jinming Li
The echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (EML4-ALK) rearrangement is an important biomarker that plays a pivotal role in therapeutic decision making for non-small-cell lung cancer (NSCLC) patients. Ensuring accuracy and reproducibility of EML4-ALK testing by fluorescence in situ hybridization, immunohistochemistry, RT-PCR, and next-generation sequencing requires reliable reference materials for monitoring assay sensitivity and specificity...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28731050/genomic-abnormalities-in-invasive-endocervical-adenocarcinoma-correlate-with-pattern-of-invasion-biologic-and-clinical-implications
#18
Anjelica Hodgson, Yutaka Amemiya, Arun Seth, Matthew Cesari, Bojana Djordjevic, Carlos Parra-Herran
The pattern-based classification system for HPV-related endocervical adenocarcinoma, which classifies tumors based on the destructiveness of stromal invasion, is predictive of the risk of nodal metastases and adverse outcome. Previous studies have demonstrated clinically important molecular alterations in endocervical adenocarcinoma, including KRAS and PIK3CA mutations; however, correlation between the molecular landscape and pathological variables including pattern of invasion has not been thoroughly explored...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28731042/molecular-alterations-of-coexisting-thyroid-papillary-carcinoma-and-anaplastic-carcinoma-identification-of-tert-mutation-as-an-independent-risk-factor-for-transformation
#19
Naoki Oishi, Tetsuo Kondo, Aya Ebina, Yukiko Sato, Junko Akaishi, Rumi Hino, Noriko Yamamoto, Kunio Mochizuki, Tadao Nakazawa, Hiroshi Yokomichi, Koichi Ito, Yuichi Ishikawa, Ryohei Katoh
Thyroid papillary carcinoma is the most common endocrine neoplasm and generally carries a favorable prognosis. However, a small subset of papillary carcinomas transforms into anaplastic carcinoma, an undifferentiated cancer with a dismal prognosis. Recent studies using next-generation sequencing revealed the genomic landscape of papillary carcinoma and anaplastic carcinoma. However, risk factors for anaplastic transformation in papillary carcinoma remain obscure. In the present study, we investigated molecular alterations of papillary carcinoma and anaplastic carcinoma components in 27 tumors in which anaplastic carcinoma coexisted with antecedent papillary carcinoma...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28730480/identification-and-validation-of-driver-kinases-from-next-generation-sequencing-data
#20
Andri Leonidou, Barrie Peck, Rachael Natrajan
It is well appreciated that activating mutations in kinase genes result in kinome reprogramming that leads to altered downstream signaling networks that drive tumor progression. Indeed small-molecule inhibition of activated kinases has heralded the wave of precision medicine in the past decade. The advent of next-generation sequencing has identified a plethora of potentially activating mutations and fusion genes in previously unreported kinase genes that can potentially be developed as targeted therapies. However, the bottleneck in the translation of these alterations into clinically useful therapies lies in their functional validation...
2017: Methods in Molecular Biology
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