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Mutation analysis biomarkers cancer

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https://www.readbyqxmd.com/read/28430623/clinical-efficacy-of-icotinib-in-lung-cancer-patients-with-different-egfr-mutation-status-a-meta-analysis
#1
REVIEW
Jian Qu, Ya-Nan Wang, Ping Xu, Da-Xiong Xiang, Rui Yang, Wei Wei, Qiang Qu
Icotinib is a novel and the third listed epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which exerts a good anti-tumor efficacy on non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs has been shown to be associated with the EGFR mutation status, especially exon 19 deletion (19Del) and exon 21 L858R mutation. Therefore, a meta-analysis was performed to assess the efficacy of icotinib in NSCLC patients harboring EGFR mutations (19Del or L858R) and wild type (19Del and L858R loci wild type)...
February 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427160/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#2
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420421/analysis-of-100-000-human-cancer-genomes-reveals-the-landscape-of-tumor-mutational-burden
#3
Zachary R Chalmers, Caitlin F Connelly, David Fabrizio, Laurie Gay, Siraj M Ali, Riley Ennis, Alexa Schrock, Brittany Campbell, Adam Shlien, Juliann Chmielecki, Franklin Huang, Yuting He, James Sun, Uri Tabori, Mark Kennedy, Daniel S Lieber, Steven Roels, Jared White, Geoffrey A Otto, Jeffrey S Ross, Levi Garraway, Vincent A Miller, Phillip J Stephens, Garrett M Frampton
BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. METHODS: In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome...
April 19, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28411881/overexpression-of-mutl-homolog-1-and-muts-homolog-2-proteins-have-reversed-prognostic-implications-for-stage-i-ii-colon-cancer-patients
#4
Shih-Chiang Huang, Shiu-Feng Huang, Ya-Ting Chen, Yu Chang, Yu-Ting Chiu, Il-Chi Chang, Hong-Dar Isaac Wu, Jinn-Shiun Chen
BACKGROUND: The outcome of colon cancer patients without lymph node metastasis is heterogeneous. Searching for new prognostic markers is warranted. METHODS: One hundred twenty stage I-II colon cancer patients who received complete surgical excision during 1995-2004 were selected for this biomarker study. Immunohistochemical method was used to assess p53, epidermal growth factor receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing. RESULTS: Thirty three patients (27...
February 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28404093/somatic-pole-proofreading-domain-mutation-immune-response-and-prognosis-in-colorectal-cancer-a-retrospective-pooled-biomarker-study
#5
Enric Domingo, Luke Freeman-Mills, Emily Rayner, Mark Glaire, Sarah Briggs, Louis Vermeulen, Evelyn Fessler, Jan Paul Medema, Arnoud Boot, Hans Morreau, Tom van Wezel, Gerrit-Jan Liefers, Ragnhild A Lothe, Stine A Danielsen, Anita Sveen, Arild Nesbakken, Inti Zlobec, Alessandro Lugli, Viktor H Koelzer, Martin D Berger, Sergi Castellví-Bel, Jenifer Muñoz, Marco de Bruyn, Hans W Nijman, Marco Novelli, Kay Lawson, Dahmane Oukrif, Eleni Frangou, Peter Dutton, Sabine Tejpar, Mauro Delorenzi, Rachel Kerr, David Kerr, Ian Tomlinson, David N Church
BACKGROUND: Precision cancer medicine depends on defining distinct tumour subgroups using biomarkers that may occur at very modest frequencies. One such subgroup comprises patients with exceptionally mutated (ultramutated) cancers caused by mutations that impair DNA polymerase epsilon (POLE) proofreading. METHODS: We examined the association of POLE proofreading domain mutation with clinicopathological variables and immune response in colorectal cancers from clinical trials (VICTOR, QUASAR2, and PETACC-3) and colorectal cancer cohorts (Leiden University Medical Centre 1 and 2, Oslo 1 and 2, Bern, AMC-AJCC-II, and Epicolon-1)...
November 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28401338/serum-he4-is-correlated-to-prognostic-factors-and-survival-in-patients-with-endometrial-cancer
#6
A Stiekema, Car Lok, C M Korse, W J van Driel, V van der Noort, G G Kenter, K K Van de Vijver
The extent of surgery and the decision for adjuvant treatment in patients with endometrial cancer (EC) depend on the presence of risk factors for lymph node metastases and disease recurrence. Postoperative markers such as myometrial infiltration and specific mutations can select patients for adjuvant treatment but will not influence surgical planning. A biomarker stratifying patients into low-risk and high-risk groups before surgery could identify patients who benefit from more extensive surgery. Therefore, we evaluated the correlation of serum biomarker HE4 with clinical and recently identified prognostic pathological variables and survival...
April 11, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28384037/pi3k-overexpression-and-pik3ca-mutations-are-associated-with-age-tumor-staging-and-other-clinical-characteristics-in-chinese-patients-with-esophageal-squamous-cell-carcinoma
#7
Jing-Wei Lin, Xu Li, Ming-Lian Qiu, Rong-Gang Luo, Jian-Bo Lin, Bo Liu
AIMS: The aim of this study was to investigate the association of PI3K expression and PIK3CA mutations with various clinical features in Chinese patients diagnosed with esophageal squamous cell carcinoma (ESCC). METHODS: The study included 112 patients diagnosed with ESCC from Jan 2013 to Dec 2015. Immunohistochemistry was used to determine the expression of PI3K. PIK3CA mutations were determined by sequencing. Statistical analysis was done using SPSS 19.0 software...
April 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28382702/post-surgery-circulating-free-tumor-dna-is-a-predictive-biomarker-for-relapse-of-lung-cancer
#8
Wenwei Hu, Yang Yang, Longzhen Zhang, Jianxin Yin, Jingwei Huang, Lei Huang, Hua Gu, Gening Jiang, Jianmin Fang
Cancer cells release DNA fragments into plasma as circulating free DNA (cfDNA). However, quantitative measurement of tumor-derived DNA in cfDNA remains challenge. The purpose of this study was to quantitatively assess tumor-derived DNA in lung cancer patients. By optimizing competitive allele-specific TaqMan PCR (CAST-PCR), we assessed the copy number of mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) alleles in the pre/post surgery plasma of 168 lung cancer patients...
April 5, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28381546/expression-of-neuroendocrine-factor-vgf-in-lung-cancer-cells-confers-resistance-to-egfr-kinase-inhibitors-and-triggers-epithelial-to-mesenchymal-transition
#9
Hwang Wen, Yu-Fan Chiu, Ming-Han Kuo, Kuan-Lin Lee, An-Chun Lee, Chia-Cherng Yu, Junn-Liang Chang, Wen-Chien Huang, Shih-Hsin Hsiao, Sey-En Lin, Yu-Ting Chou
Mutations in EGFR drive tumor growth but render tumor cells sensitive to treatment with EGFR tyrosine kinase inhibitors (TKIs). Phenotypic alteration in epithelial-to-mesenchymal transition (EMT) has been linked to the TKI resistance in lung adenocarcinoma. However, the mechanism underlying this resistance remains unclear. Here we report that high expression of a neuroendocrine factor termed VGF induces the transcription factor TWIST1 to facilitate TKI resistance, EMT, and cancer dissemination in a subset of lung adenocarcinoma cells...
April 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28376230/target-and-agent-prioritization-for-the-children-s-oncology-group-national-cancer-institute-pediatric-match-trial
#10
Carl E Allen, Theodore W Laetsch, Rajen Mody, Meredith S Irwin, Megan S Lim, Peter C Adamson, Nita L Seibel, D Williams Parsons, Y Jae Cho, Katherine Janeway
Over the past decades, outcomes for children with cancer have improved dramatically through serial clinical trials based in large measure on dose intensification of cytotoxic chemotherapy for children with high-risk malignancies. Progress made through such dose intensification, in general, is no longer yielding further improvements in outcome. With the revolution in sequencing technologies and rapid development of drugs that block specific proteins and pathways, there is now an opportunity to improve outcomes for pediatric cancer patients through mutation-based targeted therapeutic strategies...
May 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28376205/association-of-uba6-specific-e2-use1-with-lung-tumorigenesis
#11
Seong-Jin Kim, Tae Hyeong Lee, Sang Hee Nam, Ji-Hong Kim, Sangho Oh, Yeon Sook Cho, Myeong Sup Lee, Sehoon Choi, Peter C W Lee
Background: The UBA6-specific E2 conjugating enzyme 1 (USE1) ubiquitin enzyme cascade is a poorly characterized arm of the ubiquitin-proteasome system. We investigated whether the UBA6-USE1 enzyme cascade plays a role in lung cancer tumorigenesis. Methods: USE1 expression was assessed in tumor-normal paired samples from 106 lung cancer patients by immunoblot. USE1 was stably overexpressed and knocked down in lung cancer cell lines to evaluate cell proliferation, colony formation, and invasion...
March 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28365952/cell-free-dna-as-biomarker-and-source-for-mutation-detection-in-primary-colorectal-cancer
#12
Aleksandra Nikolic, Marina Vlajnic, Momcilo Ristanovic, Jelena Petrovic, Ivan Dimitrijevic, Zoran Krivokapic, Dragica Radojkovic
PURPOSE: To analyze if cell-free (cf)DNA levels and the presence of KRAS and BRAF mutations in serum could be used as diagnostic biomarkers in patients with primary colorectal cancer (CRC). METHODS: This study included 92 individuals who were operated due to primary CRC (N=52;study group) and to hemorrhoids (N=40;control group). Serum cfDNA levels were measured with real-time PCR (RT-PCR) using PicoGreen dsDNA quantitation reagent. Colorectal tissue and related blood and serum samples taken at the time of surgery were subjected to DNA extraction and analysis of KRAS and BRAF mutations based on multiplex SNaPshot assay and DNA sequencing...
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28359318/24h-gene-variation-effect-of-combined-bevacizumab-erlotinib-in-advanced-non-squamous-non-small-cell-lung-cancer-using-exon-array-blood-profiling
#13
Florent Baty, Markus Joerger, Martin Früh, Dirk Klingbiel, Francesco Zappa, Martin Brutsche
BACKGROUND: The SAKK 19/05 trial investigated the safety and efficacy of the combined targeted therapy bevacizumab and erlotinib (BE) in unselected patients with advanced non-squamous non-small cell lung cancer (NSCLC). Although activating EGFR mutations were the strongest predictors of the response to BE, some patients not harboring driver mutations could benefit from the combined therapy. The identification of predictive biomarkers before or short after initiation of therapy is therefore paramount for proper patient selection, especially among EGFR wild-types...
March 30, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28357401/computational-analysis-of-specific-microrna-biomarkers-for-noninvasive-early-cancer-detection
#14
Tianci Song, Yanchun Liang, Zhongbo Cao, Wei Du, Ying Li
Cancer is a complex disease residing in various tissues of human body, accompanied with many abnormalities and mutations in genomes, transcriptome, and epigenome. Early detection plays a crucial role in extending survival time of all major cancer types. Recent advances in microarray and sequencing techniques have given more support to identifying effective biomarkers for early detection of cancer. MicroRNAs (miRNAs) are more and more frequently used as candidates for biomarkers in cancer related studies due to their regulation of target gene expression...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28356971/elevated-microrna-125b-levels-predict-a-worse-prognosis-in-her2-positive-breast-cancer-patients
#15
Yanwei Luo, Xinye Wang, Weihong Niu, Heran Wang, Qiuyuan Wen, Songqing Fan, Ran Zhao, Zheng Li, Wei Xiong, Shuping Peng, Zhaoyang Zeng, Xiaoling Li, Guiyuan Li, Ming Tan, Ming Zhou
Breast cancer, the second most common cancer worldwide, is the leading cause of cancer-associated mortality in women, accounting for ~15% of all cancer-associated mortalities in women. The development, local invasion and metastasis of breast cancer are associated with the dysregulation and mutation of numerous genes and epigenetic mechanisms, including coding RNA and non-coding RNA, such as microRNAs (miRs/miRNAs). Previous studies have shown a dual-faced role of miR-125b in breast cancer. In the present study, a total of 221 paraffin-embedded breast cancer and 49 paraffin-embedded non-cancerous breast tissue samples were collected...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351974/mutational-spectra-of-aflatoxin-b1-in-vivo-establish-biomarkers-of-exposure-for-human-hepatocellular-carcinoma
#16
Supawadee Chawanthayatham, Charles C Valentine, Bogdan I Fedeles, Edward J Fox, Lawrence A Loeb, Stuart S Levine, Stephen L Slocum, Gerald N Wogan, Robert G Croy, John M Essigmann
Aflatoxin B1 (AFB1) and/or hepatitis B and C viruses are risk factors for human hepatocellular carcinoma (HCC). Available evidence supports the interpretation that formation of AFB1-DNA adducts in hepatocytes seeds a population of mutations, mainly G:C→T:A, and viral processes synergize to accelerate tumorigenesis, perhaps via inflammation. Responding to a need for early-onset evidence predicting disease development, highly accurate duplex sequencing was used to monitor acquisition of high-resolution mutational spectra (HRMS) during the process of hepatocarcinogenesis...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28350084/tp53-and-ret-may-serve-as-biomarkers-of-prognostic-evaluation-and-targeted-therapy-in-hepatocellular-carcinoma
#17
Song Ye, Xin-Yi Zhao, Xiao-Ge Hu, Tang Li, Qiu-Ran Xu, Huan-Ming Yang, Dong-Sheng Huang, Liu Yang
Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. Genomic analysis is conducted to identify genetic alterations in driver genes which are all druggable targets for cancer therapy. In the present study, we performed an exome sequencing of 45 driver genes in 100 paired samples from HCC patients including tumors and matched adjacent normal tissues using Illumina HiSeq 2000 platform. Non-synonymous mutations were ascertained using the iPLEX MassARRAY system and Sanger sequencing. Clinicopathological relevance with genetic variations was assessed using SPSS software...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28349822/slco1b3-screening-in-colorectal-cancer-patients-using-high-resolution-melting-analysis-method-and-immunohistochemistry
#18
Lampri Evangeli, Sainis Ioannis, Kounnis Valentinos, Mitselou Antigony, Ioachim Elli, Hatzimichael Eleftheria, Galani Vasiliki, Briasoulis Evangelos
Personalized medicine has made some major advances in colorectal cancer, but new biomarkers still remain a hot issue as an emerging tool with potential prognostic and therapeutic potential. We investigated for SLCO1B3 gene alterations and protein expression in colorectal cancer, using the novel high-resolution melting analysis technique and immunohistochemistry. Formalin-fixed paraffin-embedded tumor samples from 30 colorectal cancer patients were used. The screening for gene alterations was done by high-resolution melting analysis for all exons of SLCO1B3 gene...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28348045/stratification-of-pancreatic-ductal-adenocarcinoma-combinatorial-genetic-stromal-and-immunological-markers
#19
Erik Knudsen, Paris Vail, Uthra Balaji, Hoai Ngo, Ihab W Botros, Vladimir Makarov, Nadeem Riaz, Vinod P Balachandran, Steven D Leach, Debrah M Thompson, Timothy A Chan, Agnieszka K Witkiewicz
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is associated with an immunosuppressive milieu that supports immune system evasion and disease progression. Here, we interrogated genetic, stromal, and immunological features of PDAC to delineate impact on prognosis and to more effectively employ immunotherapy. EXPERIMENTAL DESIGN: A cohort of 109 PDAC cases annotated for overall survival was utilized as a primary discovery cohort. Gene expression analysis defined immunological subtypes of PDAC that were confirmed in the Cancer Genome Atlas data set...
March 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28337711/circulating-tumor-dna-for-mutation-detection-and-identification-of-mechanisms-of-resistance-in-non-small-cell-lung-cancer
#20
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
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