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https://www.readbyqxmd.com/read/29158875/a-gene-module-based-eqtl-analysis-prioritizing-disease-genes-and-pathways-in-kidney-cancer
#1
Mary Qu Yang, Dan Li, William Yang, Yifan Zhang, Jun Liu, Weida Tong
Clear cell renal cell carcinoma (ccRCC) is the most common and most aggressive form of renal cell cancer (RCC). The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/29156850/harness-the-synergy-between-targeted-therapy-and-immunotherapy-what-have-we-learned-and-where-are-we-headed
#2
REVIEW
Xiaoyan Liu, Qing Zhou, Yan Xu, Minjiang Chen, Jing Zhao, Mengzhao Wang
Since the introduction of imatinib for the treatment of chronic myelogenous leukemia, several oncogenic mutations have been identified in various malignancies that can serve as targets for therapy. More recently, a deeper insight into the mechanism of antitumor immunity and tumor immunoevasion have facilitated the development of novel immunotherapy agents. Certain targeted agents have the ability of inhibiting tumor growth without causing severe lymphocytopenia and amplifying antitumor immune response by increasing tumor antigenicity, enhancing intratumoral T cell infiltration, and altering the tumor immune microenvironment, which provides a rationale for combining targeted therapy with immunotherapy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156722/whole-exome-sequencing-reveals-novel-mutations-and-epigenetic-regulation-in-hypopharyngeal-carcinoma
#3
Ping Wu, Honglong Wu, Yaoyun Tang, Shi Luo, Xing Fang, Chubo Xie, Jian He, Suping Zhao, Xiaofeng Wang, Jiajia Xu, Xi Chen, Dongfang Li, Huanming Yang, Jian Wang
Hypopharyngeal cancer (HPC) frequently presents at an advanced stage, resulting in poor prognosis. Although combined surgical therapy and chemoradiotherapy have improved the survival for patients with HPC over the past 3 decades, the mortality rate in late-stage diagnosis of HPC is unsatisfactory. In this study, we performed whole-exome sequencing (WES) of 23 hypopharyngeal tumor and paired adjacent normal tissue to identify novel candidate driver genes associated with hypopharyngeal carcinoma. We identified several copy number variants (CNVs) and 15 somatic mutation genes that were associated with hypopharyngeal carcinoma...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156578/pancreatic-cancer-molecular-characterization-clonal-evolution-and-cancer-stem-cells
#4
REVIEW
Elvira Pelosi, Germana Castelli, Ugo Testa
Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of <10%. PDAC arises from different types of non-invasive precursor lesions: intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development...
November 18, 2017: Biomedicines
https://www.readbyqxmd.com/read/29153898/the-significance-of-the-pd-l1-expression-in-non-small-cell-lung-cancer-trenchant-double-swords-as-predictive-and-prognostic-markers
#5
REVIEW
Kazuki Takada, Gouji Toyokawa, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
Lung cancer is the leading cause of death due to cancer worldwide. Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes. Despite advances in such therapies, the prognosis of patients with NSCLC without driver oncogene mutations remains poor. Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC...
October 28, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29152593/resistance-is-futile-overcoming-resistance-to-targeted-therapies-in-lung-adenocarcinoma
#6
Dana S Neel, Trever G Bivona
The advent of genomics has led to the identification of specific "driver" mutations in oncogenic kinases, and the development of targeted small molecule inhibitors to block their tumor-driving functions. These specific inhibitors have been a clinical success, and often significantly prolong the lives of individuals with cancer. Inevitably, however, the treated tumors recur as resistance to these targeted therapies develops. Here, we review the major mechanisms by which a cancer cell can evade targeted therapy, focusing on mechanisms of resistance to kinase inhibitors in lung cancer...
2017: NPJ Precis Oncol
https://www.readbyqxmd.com/read/29152094/xenotransplantation-of-pediatric-low-grade-gliomas-confirms-the-enrichment-of-braf-v600e-mutation-and-preservation-of-cdkn2a-deletion-in-a-novel-orthotopic-xenograft-mouse-model-of-progressive-pleomorphic-xanthoastrocytoma
#7
Mari Kogiso, Lin Qi, Holly Lindsay, Yulun Huang, Xiumei Zhao, Zhigang Liu, Frank K Braun, Yuchen Du, Huiyuan Zhang, Goeun Bae, Sibo Zhao, Sarah G Injac, Mary Sobieski, David Brunell, Vidya Mehta, Diep Tran, Jeffrey Murray, Patricia A Baxter, Xiao-Jun Yuan, Jack M Su, Adekunle Adesina, Laszlo Perlaky, Murali Chintagumpala, D Williams Parsons, Ching C Lau, Clifford C Stephan, Xinyan Lu, Xiao-Nan Li
To identify cellular and molecular changes that driver pediatric low grade glioma (PLGG) progression, we analyzed putative cancer stem cells (CSCs) and evaluated key biological changes in a novel and progressive patient-derived orthotopic xenograft (PDOX) mouse model. Flow cytometric analysis of 22 PLGGs detected CD133(+) (<1.5%) and CD15(+) (20.7 ± 28.9%) cells, and direct intra-cranial implantation of 25 PLGGs led to the development of 1 PDOX model from a grade II pleomorphic xanthoastrocytoma (PXA). While CSC levels did not correlate with patient tumor progression, neurosphere formation and in vivo tumorigenicity, the PDOX model, IC-3635PXA, reproduced key histological features of the original tumor...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152076/profiling-tumour-heterogeneity-through-circulating-tumour-dna-in-patients-with-pancreatic-cancer
#8
Patricia Adamo, Caroline M Cowley, Christopher P Neal, Vilas Mistry, Karen Page, Ashley R Dennison, John Isherwood, Robert Hastings, JinLi Luo, David A Moore, Pringle J Howard, Martins L Miguel, Catrin Pritchard, Margaret Manson, Jacqui A Shaw
The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed late so that surgery is rarely curative. Earlier detection could significantly increase the likelihood of successful treatment and improve survival. The aim of the study was to provide proof of principle that point mutations in key cancer genes can be identified by sequencing circulating free DNA (cfDNA) and that this could be used to detect early PDACs and potentially, premalignant lesions, to help target early effective treatment. Targeted next generation sequencing (tNGS) analysis of mutation hotspots in 50 cancer genes was conducted in 26 patients with PDAC, 14 patients with chronic pancreatitis (CP) and 12 healthy controls with KRAS status validated by digital droplet PCR...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152060/inhibition-of-chk1-sensitizes-ewing-sarcoma-cells-to-the-ribonucleotide-reductase-inhibitor-gemcitabine
#9
Kelli L Goss, Stacia L Koppenhafer, Kathryn M Harmoney, William W Terry, David J Gordon
Ewing sarcoma is a bone and soft tissue sarcoma that occurs in children and young adults. The EWS-FLI1 gene fusion is the driver mutation in most Ewing sarcoma tumors and functions, in part, as an aberrant transcription factor. We recently identified that Ewing sarcoma cells are sensitive to inhibition of ribonucleotide reductase (RNR), which catalyzes the formation of deoxyribonucleotides from ribonucleotides. In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149658/evaluating-casama-contextualized-semantic-maps-for-summarization-of-lung-cancer-studies
#10
Jean I Garcia-Gathright, Nicholas J Matiasz, Carlos Adame, Karthik V Sarma, Lauren Sauer, Nova F Smedley, Marshall L Spiegel, Jennifer Strunck, Edward B Garon, Ricky K Taira, Denise R Aberle, Alex A T Bui
OBJECTIVE: It is crucial for clinicians to stay up to date on current literature in order to apply recent evidence to clinical decision making. Automatic summarization systems can help clinicians quickly view an aggregated summary of literature on a topic. Casama, a representation and summarization system based on "contextualized semantic maps," captures the findings of biomedical studies as well as the contexts associated with patient population and study design. This paper presents a user-oriented evaluation of Casama in comparison to a context-free representation, SemRep...
November 3, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/29149178/drivers-of-genetic-diversity-in-secondary-metabolic-gene-clusters-within-a-fungal-species
#11
Abigail L Lind, Jennifer H Wisecaver, Catarina Lameiras, Philipp Wiemann, Jonathan M Palmer, Nancy P Keller, Fernando Rodrigues, Gustavo H Goldman, Antonis Rokas
Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence...
November 17, 2017: PLoS Biology
https://www.readbyqxmd.com/read/29148847/emerging-therapeutic-targets-in-myeloproliferative-neoplasms-and-peripheral-t-cell-leukemia-and-lymphomas
#12
Anna Orlova, Bettina Wingelhofer, Heidi A Neubauer, Barbara Maurer, Angelika Berger-Becvar, György Miklós Keserű, Patrick T Gunning, Peter Valent, Richard Moriggl
Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations of chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148397/evolutionary-context-of-non-sorbitol-fermenting-shiga-toxin-producing-escherichia-coli-o55-h7
#13
Kyle Schutz, Lauren A Cowley, Sharif Shaaban, Anne Carroll, Eleanor McNamara, David L Gally, Gauri Godbole, Claire Jenkins, Timothy J Dallman
In July 2014, an outbreak of Shiga toxin-producing Escherichia coli (STEC) O55:H7 in England involved 31 patients, 13 (42%) of whom had hemolytic uremic syndrome. Isolates were sequenced, and the sequences were compared with publicly available sequences of E. coli O55:H7 and O157:H7. A core-genome phylogeny of the evolutionary history of the STEC O55:H7 outbreak strain revealed that the most parsimonious model was a progenitor enteropathogenic O55:H7 sorbitol-fermenting strain, lysogenized by a Shiga toxin (Stx) 2a-encoding phage, followed by loss of the ability to ferment sorbitol because of a non-sense mutation in srlA...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29146060/clinicopathologic-correlation-of-programmed-death-ligand-1-expression-in-non-small-cell-lung-carcinomas-a-report-from-india
#14
Archana George Vallonthaiel, Prabhat Singh Malik, Varsha Singh, Vinay Kumar, Sunil Kumar, Mehar Chand Sharma, Sandeep Mathur, Sudheer Arava, Randeep Guleria, Deepali Jain
INTRODUCTION: Increased expression of Programmed death ligand-1 (PD-L1) on cancer cells and immune cells predict response to PD-1/PDL1 inhibitors. Data regarding frequency and pattern of PD-L1 expression in NSCLC from India is not available. OBJECTIVES: To analyse PD-L1 expression on tumour cells (TC) and immune cells (IC) and to correlate PD-L1 expression with baseline clinico-pathological characteristics, oncogenic drivers and outcome data. MATERIALS AND METHODS: PD-L1 expression on tumour cells and immune cells was analysed...
December 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29144541/genetic-landscape-of-papillary-thyroid-carcinoma-in-the-chinese-population
#15
Jialong Liang, Wanshi Cai, Dongdong Feng, Huajing Teng, Fengbiao Mao, Yi Jiang, Shanshan Hu, Xianfeng Li, Yujie Zhang, Baoguo Liu, Zhong Sheng Sun
Improvement in the clinical outcome of human cancers requires characterization of genetic alterations underlying their pathogenesis. Large-scale genomic and transcriptomic characterization of papillary thyroid carcinomas (PTCs) in Western populations has revealed multiple oncogenic drivers which are essential for understanding pathogenic mechanisms of this disease; while so far, the genetic landscape in Chinese patients with PTC remains uncharacterized. Here, we conducted a largescale genetic analysis of PTCs from patients in China to determine the mutational landscape of this cancer...
November 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29143801/novel-molecular-challenges-in-targeting-anaplastic-lymphoma-kinase-in-alk-expressing-human-cancers
#16
REVIEW
Abdulraheem Alshareef
Targeting anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase receptor initially identified as a potent oncogenic driver in anaplastic large-cell lymphoma (ALCL) in the form of nucleophosmin (NPM)-ALK fusion protein, using tyrosine kinase inhibitors has shown to be a promising therapeutic approach for ALK-expressing tumors. However, clinical resistance to ALK inhibitors invariably occurs, and the molecular mechanisms are incompletely understood. Recent studies have clearly shown that clinical resistance to ALK inhibitors is a multifactorial and complex mechanism...
October 28, 2017: Cancers
https://www.readbyqxmd.com/read/29143738/bladder-cancer-associated-mutations-in-rxra-activate-peroxisome-proliferator-activated-receptors-to-drive-urothelial-proliferation
#17
Angela M Halstead, Chiraag D Kapadia, Jennifer Bolzenius, Clarence E Chu, Andrew Schriefer, Lukas D Wartman, Gregory R Bowman, Vivek K Arora
RXRA regulates transcription as part of a heterodimer with 14 other nuclear receptors, including the peroxisome proliferator-activated receptors (PPARs). Analysis from the TCGA raised the possibility that hyperactive PPAR signaling, either due to PPAR gamma gene amplification or RXRA hot-spot mutation (S427F/Y) drives 20-25% of human bladder cancers. Here we characterize mutant RXRA, demonstrating it induces enhancer/promoter activity in the context of RXRA/PPAR heterodimers in human bladder cancer cells. Structure-function studies indicate that the RXRA substitution allosterically regulates the PPAR AF2 domain via an aromatic interaction with the terminal tyrosine found in PPARs...
November 16, 2017: ELife
https://www.readbyqxmd.com/read/29143497/detection-and-monitoring-of-driver-mutations-by-next-generation-sequencing-in-squamous-cell-lung-cancer-patient-and-possible-predictive-biomarker-of-third-generation-egfr-tyrosine-kinase-inhibitors
#18
Xiaoyan Shen, Jie Shen, Hang Zhang, Yuxin Cheng, Yang Yang, Jiahui Gao, Yu Zhang, Rutian Li, Baorui Liu, Lifeng Wang
Driver mutation detection and the development of targeted drugs have significantly improved survival of advanced lung adenocarcinoma patients with driver mutations. However, we still lack understanding of druggable mutations in patients with advanced squamous cell lung cancer (SQCLC). Less than 10% of SQCLC patients have EGFR gene mutations, thus we have limited knowledge of biological molecular changes with first generation EGFR-tyrosine kinase inhibitor (TKI) resistance. We report a case of an SQCLC patient treated with first-line platinum-doublet chemotherapy...
November 16, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29142125/emergence-of-double-and-triple-gene-reassortant-g1p-8-rotaviruses-possessing-a-ds-1-like-backbone-post-rotavirus-vaccine-introduction-in-malawi
#19
Khuzwayo C Jere, Chrispin Chaguza, Naor Bar-Zeev, Jenna Lowe, Chikondi Peno, Benjamin Kumwenda, Osamu Nakagomi, Jacqueline E Tate, Umesh D Parashar, Robert S Heyderman, Neil French, Nigel A Cunliffe, Iturriza-Gomara Miren
To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunisation programmes. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix™) into its immunisation schedule in 2012. Utilising a surveillance platform of hospitalised rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 - 2012) and after (2013 - 2014) vaccine introduction. Analysis of whole genomes obtained through next generation sequencing revealed that all randomly-selected pre-vaccine G1P[8] strains sequenced (n=32) possessed a Wa-like genetic constellation, whereas post-vaccine G1P[8] strains (n=18) had a DS-1-like constellation...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29138255/complex-history-and-differentiation-patterns-of-the-t-haplotype-a-mouse-meiotic-driver
#20
Reka K Kelemen, Beatriz Vicoso
The t-haplotype, a mouse meiotic driver found on chromosome 17, has been a model for autosomal segregation distortion for close to a century, but several questions remain regarding its biology and evolutionary history. A recently published set of population genomics resources for wild mice includes several individuals heterozygous for the t-haplotype, which we use to characterize this selfish element at the genomic and transcriptomic level. Our results show that large sections of the t-haplotype have been replaced by standard homologous sequences, possibly due to occasional events of recombination, and that this complicates the inference of its history...
November 14, 2017: Genetics
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