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Mutation analysis biomarkers cancer

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https://www.readbyqxmd.com/read/28337711/circulating-tumor-dna-for-mutation-detection-and-identification-of-mechanisms-of-resistance-in-non-small-cell-lung-cancer
#1
REVIEW
Kay T Yeung, Soham More, Brian Woodward, Victor Velculescu, Hatim Husain
Targeted therapies have changed the treatment landscape of non-small cell lung cancer over the past decade. Analyses of cell free circulating tumor DNA (ctDNA) provide a non-invasive and robust approach for cancer diagnosis and prognosis, real-time monitoring of treatment response, and the identification of appropriate therapeutic targets based on the detection of tumor genetic aberrations. Recent improvements in the sensitivity, specificity, and feasibility of ctDNA detection assays allow the possibility for implementation into clinical practice...
March 24, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28334878/high-expression-of-ire1-in-lung-adenocarcinoma-is-associated-with-a-lower-rate-of-recurrence
#2
Toshio Sakatani, Keita Maemura, Noriko Hiyama, Yosuke Amano, Kousuke Watanabe, Hidenori Kage, Masashi Fukayama, Jun Nakajima, Yutaka Yatomi, Takahide Nagase, Daiya Takai
Objective: Recent reports have shown that endoplasmic reticulum stress is associated with cancer. However, the impacts of endoplasmic reticulum stress on the prognosis of lung cancer are unknown. Therefore, in this study, we sought to reveal the relationship between the expression of endoplasmic reticulum stress-related genes (endoplasmic reticulum oxidoreductase 1L, protein kinase RNA-like endoplasmic reticulum kinase, activating transcription factor 6 and inositol-requiring kinase 1) and the outcome of lung adenocarcinoma...
March 17, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28328955/treatment-monitoring-in-metastatic-colorectal-cancer-patients-by-quantification-and-kras-genotyping-of-circulating-cell-free-dna
#3
Andreas W Berger, Daniel Schwerdel, Hanna Welz, Ralf Marienfeld, Stefan A Schmidt, Alexander Kleger, Thomas J Ettrich, Thomas Seufferlein
Treatment of metastatic colorectal cancer (CRC) has continuously improved over the last decade. However, disease monitoring remains underdeveloped and mostly dependent on imaging e.g. RECIST 1.1 criteria. The genetic landscape of individual cancers and subsequently occurring treatment-induced evolution remain neglected in current surveillance strategies. Novel biomarkers demand minimally invasive and repetitive tracking of the cancer mutagenome for therapy stratification and to make prognostic predictions. Carcinoembryonic antigen (CEA), a routinely used tumor marker for CRC, does not meet these goals and thus prevents its use as a reliable monitoring tool...
2017: PloS One
https://www.readbyqxmd.com/read/28327601/bcip-a-gene-centered-platform-for-identifying-potential-regulatory-genes-in-breast-cancer
#4
Jiaqi Wu, Shuofeng Hu, Yaowen Chen, Zongcheng Li, Jian Zhang, Hanyu Yuan, Qiang Shi, Ningsheng Shao, Xiaomin Ying
Breast cancer is a disease with high heterogeneity. Many issues on tumorigenesis and progression are still elusive. It is critical to identify genes that play important roles in the progression of tumors, especially for tumors with poor prognosis such as basal-like breast cancer and tumors in very young women. To facilitate the identification of potential regulatory or driver genes, we present the Breast Cancer Integrative Platform (BCIP, http://omics.bmi.ac.cn/bcancer/). BCIP maintains multi-omics data selected with strict quality control and processed with uniform normalization methods, including gene expression profiles from 9,005 tumor and 376 normal tissue samples, copy number variation information from 3,035 tumor samples, microRNA-target interactions, co-expressed genes, KEGG pathways, and mammary tissue-specific gene functional networks...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28319896/a-dynamic-sandwich-assay-on-magnetic-beads-for-selective-detection-of-single-nucleotide-mutations-at-room-temperature
#5
Junxiu Wang, Guoliang Xiong, Liang Ma, Shihui Wang, Xu Zhou, Lei Wang, Lehui Xiao, Xin Su, Changyuan Yu
Single-nucleotide mutation (SNM) has proven to be associated with a variety of human diseases. Development of reliable methods for the detection of SNM is crucial for molecular diagnosis and personalized medicine. The sandwich assays are widely used tools for detecting nucleic acid biomarkers due to their low cost and rapid signaling. However, the poor hybridization specificity of signal probe at room temperature hampers the discrimination of mutant and wild type. Here, we demonstrate a dynamic sandwich assay on magnetic beads for SNM detection based on the transient binding between signal probe and target...
March 12, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28301567/integrated-analysis-of-promoter-mutation-methylation-and-expression-of-akt1-gene-in-chinese-breast-cancer-patients
#6
Jianfu Heng, Xinwu Guo, Wenhan Wu, Yue Wang, Guoli Li, Ming Chen, Limin Peng, Shouman Wang, Lizhong Dai, Lili Tang, Jun Wang
BACKGROUND: As downstream mediators of PI3K /PTEN /AKT /mTORC1 pathway, the AKT isoforms play critical roles in tumorgenesis. Although the pleiotropic effects of AKT1 in breast cancer have been reported, the genetic and epigenetic characteristics of AKT1 promoter region in breast cancer remains to be identified. In this study we aimed to investigate the promoter mutation spectrum, methylation and gene expression pattern of AKT1 and their relationship with breast cancer. METHODS: By using PCR target sequence enrichment and next-generation sequencing technology, we sequenced AKT1 promoter region in pairs of breast tumor and normal tissues from 95 unselected Chinese breast cancer patients...
2017: PloS One
https://www.readbyqxmd.com/read/28290700/metabolic-response-to-everolimus-in-patient-derived-triple-negative-breast-cancer-xenografts
#7
Leslie R Euceda, Deborah K Hill, Endre Stokke, Rana Hatem, Rania El Botty, Ivan Bièche, Elisabetta Marangoni, Tone F Bathen, Siver A Moestue
Patients with triple negative breast cancer (TNBC) are unresponsive to endocrine and anti-HER2 pharmacotherapy, limiting their therapeutic options to chemotherapy. TNBC is frequently associated with abnormalities in the PI3K/AKT/mTOR signaling pathway; drugs targeting this pathway are currently being evaluated in these patients. However, response is variable, partly due to heterogeneity within TNBC, conferring a need to identify biomarkers predicting response and resistance to targeted therapy. In this study, we used a metabolomics approach to assess response to the mTOR inhibitor everolimus in a panel of TNBC patient-derived xenografts (PDX) (n=103 animals)...
March 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28288572/a-multi-center-phase-ii-study-and-biomarker-analysis-of-combined-cetuximab-and-modified-folfiri-as-second-line-treatment-in-patients-with-metastatic-gastric-cancer
#8
Xin Liu, Weijian Guo, Wen Zhang, Jiliang Yin, Jun Zhang, Xiaodong Zhu, Tianshu Liu, Zhiyu Chen, Biyun Wang, Jianhua Chang, Fangfang Lv, Xiaonan Hong, Huijie Wang, Jialei Wang, Xinmin Zhao, Xianghua Wu, Jin Li
BACKGROUND: To evaluate the efficacy of cetuximab combined with modified FOLFIRI (mFOLFIRI) as a second-line treatment in metastatic gastric cancer patients and to identify potential biomarkers of clinical outcomes. METHODS: All 61 patients received an initial intravenous (IV) dose of cetuximab (400 mg/m(2)) and weekly doses (250 mg/m(2)) thereafter, starting on day 1. On day 2 of each 14-day period, patients received IV irinotecan (180 mg/m(2)), leucovorin (200 mg/m(2)), and an IV bolus dose of 5-FU (400 mg/m(2)) followed by a continuous infusion of 5-FU (2400 mg/m(2)) for 46 h...
March 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28280610/investigation-of-the-human-h3-3b-h3f3b-gene-expression-as-a-novel-marker-in-patients-with-colorectal-cancer
#9
Habib Allah Ayoubi, Frouzandeh Mahjoubi, Rezvan Mirzaei
BACKGROUND: H3.3 histone is a replacement histone subtype that is express in entire cell cycle phases and overexpress in transcriptionally active regions, promoter regions, and intergenic or intragenic regulatory elements. This histone encoded by two genes termed H3.3A (H3F3A) and H3.3B (H3F3B). Mutations of these two genes lead to some human cancers such as chondroblastoma, osteosarcoma, and epithelial ovarian cancer. The aims of this study were to quantitatively examine the expression of H3...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28278225/identification-of-endometrial-cancer-methylation-features-using-combined-methylation-analysis-methods
#10
Michael P Trimarchi, Pearlly Yan, Joanna Groden, Ralf Bundschuh, Paul J Goodfellow
BACKGROUND: DNA methylation is a stable epigenetic mark that is frequently altered in tumors. DNA methylation features are attractive biomarkers for disease states given the stability of DNA methylation in living cells and in biologic specimens typically available for analysis. Widespread accumulation of methylation in regulatory elements in some cancers (specifically the CpG island methylator phenotype, CIMP) can play an important role in tumorigenesis. High resolution assessment of CIMP for the entire genome, however, remains cost prohibitive and requires quantities of DNA not available for many tissue samples of interest...
2017: PloS One
https://www.readbyqxmd.com/read/28266251/an-integrated-analysis-of-cancer-genes-in-clear-cell-renal-cell-carcinoma
#11
Jin Li, Liping Guo, Zisheng Ai
AIM: This study was performed to detect driver genes and implement integrated analyses on these drivers in clear cell renal cell carcinoma (ccRCC). METHODS: Driver genes and pathways were predicted by OncodriveFM and Dendrix using 39,636 somatic mutations from The Cancer Genome Atlas, followed by DNA methylation, copy number variation, differential expression and survival analyses. RESULTS: Overall, 342 driver genes and 106 pathways were determined by OncodriveFM, two driver genes by Dendrix...
April 2017: Future Oncology
https://www.readbyqxmd.com/read/28256603/exome-sequencing-identifies-potentially-druggable-mutations-in-nasopharyngeal-carcinoma
#12
Yock Ping Chow, Lu Ping Tan, San Jiun Chai, Norazlin Abdul Aziz, Siew Woh Choo, Paul Vey Hong Lim, Rajadurai Pathmanathan, Noor Kaslina Mohd Kornain, Chee Lun Lum, Kin Choo Pua, Yoke Yeow Yap, Tee Yong Tan, Soo Hwang Teo, Alan Soo-Beng Khoo, Vyomesh Patel
In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28252533/derived-neutrophil-to-lymphocyte-ratio-as-a-prognostic-factor-in-patients-with-advanced-colorectal-cancer-according-to-ras-and-braf-status-a-post-hoc-analysis-of-the-mrc-coin-study
#13
Georgina Wood, Tal Grenader, Stephen Nash, Richard Adams, Richard Kaplan, David Fisher, Tim Maughan, John Bridgewater
The phase III Continuous or Intermittent (COIN) trial failed to show a benefit in overall survival (OS) of cetuximab in combination with chemotherapy for patients with metastatic colorectal cancer. High derived neutrophil to lymphocyte ratio (dNLR) has been shown to be prognostic in patients with metastatic colorectal cancer. The aim of this analysis is to evaluate dNLR as a predictive biomarker of the survival according to RAS and BRAF mutations status within the COIN trial. A post-hoc exploratory analysis of the COIN trial arms A and B was carried out...
March 1, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28251929/transposon-insertional-mutagenesis-in-mice-identifies-human-breast-cancer-susceptibility-genes-and-signatures-for-stratification
#14
Liming Chen, Piroon Jenjaroenpun, Andrea Mun Ching Pillai, Anna V Ivshina, Ghim Siong Ow, Motakis Efthimios, Tang Zhiqun, Tuan Zea Tan, Song-Choon Lee, Keith Rogers, Jerrold M Ward, Seiichi Mori, David J Adams, Nancy A Jenkins, Neal G Copeland, Kenneth Hon-Kim Ban, Vladimir A Kuznetsov, Jean Paul Thiery
Robust prognostic gene signatures and therapeutic targets are difficult to derive from expression profiling because of the significant heterogeneity within breast cancer (BC) subtypes. Here, we performed forward genetic screening in mice using Sleeping Beauty transposon mutagenesis to identify candidate BC driver genes in an unbiased manner, using a stabilized N-terminal truncated β-catenin gene as a sensitizer. We identified 134 mouse susceptibility genes from 129 common insertion sites within 34 mammary tumors...
March 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28237867/exploratory-analysis-of-biomarkers-associated-with-clinical-outcomes-from-the-study-of-lenvatinib-in-differentiated-cancer-of-the-thyroid
#15
Makoto Tahara, Martin Schlumberger, Rossella Elisei, Mouhammed Amir Habra, Naomi Kiyota, Ralf Paschke, Corina E Dutcus, Taro Hihara, Shannon McGrath, Mark Matijevic, Tadashi Kadowaki, Yasuhiro Funahashi, Steven I Sherman
BACKGROUND: Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in the phase III Study of (E7080) LEnvatinib in differentiated Cancer of the Thyroid (SELECT) of patients with radioiodine-refractory differentiated thyroid cancer. This exploratory analysis investigated potential predictive biomarkers of lenvatinib efficacy and target engagement. PATIENTS AND METHODS: Circulating cytokine/angiogenic factors (CAFs) in blood samples collected at baseline and throughout treatment were analysed from patients randomised to receive lenvatinib or placebo from August 5, 2011 to October 4, 2012...
February 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28231576/molecular-markers-involved-in-tumorigenesis-of-thyroid-carcinoma-focus-on-aggressive-histotypes
#16
Gustavo C Penna, Fernanda Vaisman, Mario Vaisman, Manuel Sobrinho-Simões, Paula Soares
Thyroid cancer derived from follicular cells (TCDFC) comprises well-differentiated (papillary and follicular) carcinoma, poorly differentiated carcinoma, and anaplastic carcinoma. Papillary thyroid carcinoma is the most common endocrine cancer, and its incidence is steadily increasing. Lethality and aggressiveness of TCDFC is inversely correlated with differentiation degree. In this review, an emphasis has been put on molecular markers involved in tumorigenesis of thyroid carcinoma with a focus on aggressive histotypes and the role of such biomarkers in predicting thyroid cancer outcome...
2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28230825/molecular-markers-of-apoptosis-in-cancer-patients-exposed-to-ionizing-radiation-the-post-chornobyl-view
#17
A A Philchenkov, E K Balcer-Kubiczek
During the past three decades, the deleterious consequences of Chornobyl accident including carcinogenic effects in the people who were accidentally exposed to radiation have been intensively studied. In particular, recent studies provided increased knowledge of the molecular pathogenesis of thyroid tumors in children exposed to Chornobyl fallout. The risk of several forms of leukemia including myelodysplastic syndromes is elevated in Chornobyl liquidators. Furthermore, the upward trends of increases in a variety of other tumors including breast cancer, cancers of central nervous system and renal cancer have been reported in the persons exposed to Chornobyl fallout...
December 2016: Experimental Oncology
https://www.readbyqxmd.com/read/28223411/pentraxin-3-is-a-pi3k-signaling-target-that-promotes-stem-cell-like-traits-in-basal-like-breast-cancers
#18
Clémence Thomas, Whitney Henry, Benjamin G Cuiffo, Anthony Y Collmann, Elisabetta Marangoni, Vanessa Benhamo, Manoj K Bhasin, Cheng Fan, Laetitia Fuhrmann, Albert S Baldwin, Charles Perou, Anne Vincent-Salomon, Alex Toker, Antoine E Karnoub
Basal-like breast cancers (BLBCs) exhibit hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway because of the frequent mutational activation of the PIK3CA catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II). However, PI3K inhibitors have had limited clinical efficacy in BLBC management because of compensatory amplification of PI3K downstream signaling loops. Therefore, identification of critical PI3K mediators is paramount to the development of effective BLBC therapeutics...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28223274/long-term-responders-on-olaparib-maintenance-in-high-grade-serous-ovarian-cancer-clinical-and-molecular-characterization
#19
Stephanie Lheureux, Zhongwu Lai, Brian A Dougherty, Sarah Runswick, Darren Hodgson, Kirsten M Timms, Jerry S Lanchbury, Stanley B Kaye, Charlie Gourley, David D L Bowtell, Elise C Kohn, Clare L Scott, Ursula A Matulonis, Tony Panzarella, Katherine Karakasis, Julia V Burnier, Blake Gilks, Mark J O'Connor, Jane D Robertson, Jonathan Ledermann, J Carl Barrett, Tony W Ho, Amit M Oza
PURPOSE: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. EXPERIMENTAL DESIGN: A comparative molecular analysis of Study 19 (NCT00753545), a randomized Phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28221868/somatic-brca1-2-recovery-as-a-resistance-mechanism-after-exceptional-response-to-poly-adp-ribose-polymerase-inhibition
#20
Stephanie Lheureux, Jeff P Bruce, Julia V Burnier, Katherine Karakasis, Patricia A Shaw, Blaise A Clarke, S Y Cindy Yang, Rene Quevedo, Tiantian Li, Mark Dowar, Valerie Bowering, Trevor J Pugh, Amit M Oza
Purpose Durable and long-term responses to the poly (ADP-ribose) polymerase inhibitor olaparib are observed in patients without BRCA1/2 mutations. However, beyond BRCA1/2 mutations, there are no approved biomarkers for olaparib in high-grade serous ovarian cancer (HGSOC). To determine mechanisms of durable response and resistance to olaparib therapy, we performed an analysis of HGSOC tumors from three patients without germline BRCA1/2 mutations who experienced exceptional responses to olaparib. Patients and Methods We performed integrated exome, low-pass genome, and RNA sequence analysis of tumors at diagnosis and upon relapse from patients with platinum-sensitive HGSOC recurrence who were treated > 5 years with olaparib therapy as a single agent...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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