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Cell free circulating cancer DNA

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https://www.readbyqxmd.com/read/28333958/targeted-deep-sequencing-of-plasma-circulating-cell-free-dna-reveals-vimentin-and-fibulin-1-as-potential-epigenetic-biomarkers-for-hepatocellular-carcinoma
#1
Reetta Holmila, Athena Sklias, David C Muller, Davide Degli Esposti, Paule Guilloreau, James Mckay, Suleeporn Sangrajrang, Petcharin Srivatanakul, Pierre Hainaut, Philippe Merle, Zdenko Herceg, Andre Nogueira da Costa
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, but is still lacking sensitive and specific biomarkers for early diagnosis and prognosis. In this study, we applied targeted massively parallel semiconductor sequencing to assess methylation on a panel of genes (FBLN1, HINT2, LAMC1, LTBP1, LTBP2, PSMA2, PSMA7, PXDN, TGFB1, UBE2L3, VIM and YWHAZ) in plasma circulating cell-free DNA (cfDNA) and to evaluate the potential of these genes as HCC biomarkers in two different series, one from France (42 HCC cases and 42 controls) and one from Thailand (42 HCC cases, 26 chronic liver disease cases and 42 controls)...
2017: PloS One
https://www.readbyqxmd.com/read/28330468/tumor-burden-monitoring-using-cell-free-tumor-dna-could-be-limited-by-tumor-heterogeneity-in-advanced-breast-cancer-and-should-be-evaluated-together-with-radiographic-imaging
#2
José Angel García-Saenz, Patricia Ayllón, Marion Laig, Daniel Acosta-Eyzaguirre, Marta García-Esquinas, Myriam Montes, Julián Sanz, Miguel Barquín, Fernando Moreno, Vanesa Garcia-Barberan, Eduardo Díaz-Rubio, Trinidad Caldes, Atocha Romero
BACKGROUND: Accurate measurement of tumor burden in breast cancer disease is essential to improve the clinical management of patients. In this study, we evaluate whether the fluctuations in the fraction of PIK3CA mutant allele correlates with tumor response according to RECIST criteria and tumor markers quantification. METHODS: Eighty six plasma samples were analyzed by digital PCR using Rare Mutation Assays for E542K, E545K and H1047R. Mutant cfDNA and tumor markers CA15-3 and CEA were compared with radiographic imaging...
March 22, 2017: BMC Cancer
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/28315952/kinetic-analysis-size-profiling-and-bioenergetic-association-of-dna-released-by-selected-cell-lines-in-vitro
#4
Janine Aucamp, Abel J Bronkhorst, Dimetrie L Peters, Hayley C Van Dyk, Francois H Van der Westhuizen, Piet J Pretorius
Although circulating DNA (cirDNA) analysis shows great promise as a screening tool for a wide range of pathologies, numerous stumbling blocks hinder the rapid translation of research to clinical practice. This is related directly to the inherent complexity of the in vivo setting, wherein the influence of complex systems of interconnected cellular responses and putative DNA sources creates a seemingly arbitrary representation of the quantitative and qualitative properties of the cirDNA in the blood of any individual...
March 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28306358/the-genetics-of-gastroesophageal-adenocarcinoma-and-the-use-of-circulating-cell-free-dna-for-disease-detection-and-monitoring
#5
Mark R Openshaw, Catherine J Richards, David S Guttery, Jacqueline A Shaw, Anne L Thomas
Gastroesophageal adenocarcinoma (GOA) is a frequently occurring cancer worldwide with a poor clinical outcome. Adenocarcinomas of the oesophagus and gastroesophageal junction have shown a recent increase in frequency, therefore there is need to increase our understanding of GOA in order to improve our ability to detect, monitor and treat the disease. Areas covered: The authors discuss the current classification of GOA in the context of recent changes in incidence. The authors also discuss developments in the understanding of disease biology and recent discoveries from whole genome and whole exome sequencing, and studies in immunotherapy...
March 17, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28285688/plasma-epidermal-growth-factor-receptor-mutation-testing-with-a-chip-based-digital-pcr-system-in-patients-with-advanced-non-small-cell-lung-cancer
#6
Norimitsu Kasahara, Hirotsugu Kenmotsu, Masakuni Serizawa, Rina Umehara, Akira Ono, Yasushi Hisamatsu, Kazushige Wakuda, Shota Omori, Kazuhisa Nakashima, Tetsuhiko Taira, Tateaki Naito, Haruyasu Murakami, Yasuhiro Koh, Keita Mori, Masahiro Endo, Takashi Nakajima, Masanobu Yamada, Masatoshi Kusuhara, Toshiaki Takahashi
OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation testing is a companion diagnostic to determine eligibility for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). Recently, plasma-based EGFR testing by digital polymerase chain reaction (dPCR), which enables accurate quantification of target DNA, has shown promise as a minimally invasive diagnostic. Here, we aimed to evaluate the accuracy of a plasma-based EGFR mutation test developed using chip-based dPCR-based detection of 3 EGFR mutations (exon 19 deletions, L858R in exon 21, and T790M in exon 20)...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28263317/identification-of-methylation-haplotype-blocks-aids-in-deconvolution-of-heterogeneous-tissue-samples-and-tumor-tissue-of-origin-mapping-from-plasma-dna
#7
Shicheng Guo, Dinh Diep, Nongluk Plongthongkum, Ho-Lim Fung, Kang Zhang, Kun Zhang
Adjacent CpG sites in mammalian genomes can be co-methylated owing to the processivity of methyltransferases or demethylases, yet discordant methylation patterns have also been observed, which are related to stochastic or uncoordinated molecular processes. We focused on a systematic search and investigation of regions in the full human genome that show highly coordinated methylation. We defined 147,888 blocks of tightly coupled CpG sites, called methylation haplotype blocks, after analysis of 61 whole-genome bisulfite sequencing data sets and validation with 101 reduced-representation bisulfite sequencing data sets and 637 methylation array data sets...
March 6, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28259476/treatment-outcomes-and-tumor-loss-of-heterozygosity-in-germline-dna-repair-deficient-prostate-cancer
#8
Matti Annala, Werner J Struss, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Daniel Khalaf, Irma-Liisa Seppälä, Alan So, Gregory Lo, Rahul Aggarwal, Eric J Small, Matti Nykter, Martin E Gleave, Kim N Chi, Alexander W Wyatt
BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA)...
March 1, 2017: European Urology
https://www.readbyqxmd.com/read/28252003/integrating-liquid-biopsies-into-the-management-of-cancer
#9
REVIEW
Giulia Siravegna, Silvia Marsoni, Salvatore Siena, Alberto Bardelli
During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly...
March 2, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28251125/the-first-liquid-biopsy-test-approved-is-it-a-new-era-of-mutation-testing-for-non-small-cell-lung-cancer
#10
Dorota Kwapisz
Specific mutations in epidermal growth factor receptor (EGFR) gene are predictive for response to the EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer patients (NSCLC). According to international guidelines, the molecular testing in patients with advanced NSCLC of a non-squamous subtype is recommended. However, obtain a tissue sample could be challenging. Liquid biopsy allows to determine patients suitable for EGFR-targeted therapy by analysis of circulating-free tumor DNA (cfDNA) in peripheral blood samples and might replace tissue biopsy...
February 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28222666/dynamic-tracing-for-epidermal-growth-factor-receptor-mutations-in-urinary-circulating-dna-in-gastric-cancer-patients
#11
Xiu-Qin Shi, Wen-Hua Xue, Song-Feng Zhao, Xiao-Jian Zhang, Wukong Sun
The mutations of epidermal growth factor receptor are detected in gastric cancer, indicating its suitability as a target for receptor tyrosine kinase inhibitors, as well as a marker for clinical outcome of chemotherapeutic treatments. However, extraction of quality tumor tissue for molecular processes remains challenging. Here, we aimed to examine the clinical relevance of urinary cell-free DNA as an alternative tumor material source used specifically for monitoring epidermal growth factor receptor mutations...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28214887/liquid-biopsy-for-cancer-circulating-tumor-cells-circulating-free-dna-or-exosomes
#12
Wei Zhang, Wenjie Xia, Zhengye Lv, Chao Ni, Yin Xin, Liu Yang
Precision medicine and personalized medicine are based on the development of biomarkers, and liquid biopsy has been reported to be able to detect biomarkers that carry information on tumor development and progression. Compared with traditional 'solid biopsy', which cannot always be performed to determine tumor dynamics, liquid biopsy has notable advantages in that it is a noninvasive modality that can provide diagnostic and prognostic information prior to treatment, during treatment and during progression. In this review, we describe the source, characteristics, technology for detection and current situation of circulating tumor cells, circulating free DNA and exosomes used for diagnosis, recurrence monitoring, prognosis assessment and medication planning...
February 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28206954/rassf1a-promoter-methylation-in-high-grade-serous-ovarian-cancer-a-direct-comparison-study-in-primary-tumors-adjacent-morphologically-tumor-cell-free-tissues-and-paired-circulating-tumor-dna
#13
Lydia Giannopoulou, Issam Chebouti, Kitty Pavlakis, Sabine Kasimir-Bauer, Evi S Lianidou
The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205231/analysis-of-ctdna-to-predict-prognosis-and-monitor-treatment-responses-in-metastatic-pancreatic-cancer-patients
#14
He Cheng, Chen Liu, Jiahao Jiang, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Zhenzhen Zhang, Jin Xu, Liang Liu, Quanxing Ni, Xianjun Yu
Cell-free circulating tumor DNA (ctDNA) in plasma has been used as a potential noninvasive biomarker for various tumors. Our study was performed to evaluate the clinical implications of ctDNA detection in patients with metastatic pancreatic cancer. First, we attempted to prospectively screen a panel of 60 genes in cell-free DNA (cfDNA) from ten metastatic pancreatic cancer patients via exome sequencing. Second, droplet digital PCR (ddPCR) was used to identify potential mutations in a cohort of 188 patients with metastatic pancreatic cancer...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28196593/liquid-biopsies-what-we-do-not-know-yet
#15
REVIEW
Alberto Bardelli, Klaus Pantel
The inherent molecular heterogeneity of metastatic tumors and the ability of cancer genomes to dynamically evolve are not properly captured by tissue specimens. Analysis of cell-free DNA and circulating tumor cells has the potential to change clinical practice by exploiting blood rather than tissue as a source of information. Liquid biopsies are already used to monitor disease response and track the emergence of drug resistance. The suitability of blood-based molecular profiles for early detection and monitoring minimal residual disease is being evaluated...
February 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28195541/assessment-of-egfr-mutation-status-using-cell-free-dna-from-bronchoalveolar-lavage-fluid
#16
Sojung Park, Jae Young Hur, Kye Young Lee, Jae Cheol Lee, Jin Kyung Rho, Sun Hwa Shin, Chang-Min Choi
BACKGROUND: Much attention has been focused on epidermal growth factor receptor (EGFR) mutation testing since the introduction of EGFR-tyrosine kinase inhibitors have improved survival in EGFR-positive lung cancer patients. Liquid biopsy using circulating tumor cells or cell-free DNA (cfDNA) has enabled less invasive testing, but requires a highly sensitive method. To date, liquid biopsy using bronchoalveolar lavage (BAL) fluid has rarely been used. METHODS: From 20 patients with lung adenocarcinoma, we isolated cfDNA from 20 samples of cell-free BAL fluid and 19 cell-free bronchial washing samples...
February 14, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28194229/circulating-and-tissue-biomarkers-in-early-stage-non-small-cell-lung-cancer
#17
Caterina Fumagalli, Fabrizio Bianchi, Paola Rafaniello Raviele, Davide Vacirca, Giovanni Bertalot, Cristiano Rampinelli, Matteo Lazzeroni, Bernardo Bonanni, Giulia Veronesi, Nicola Fusco, Massimo Barberis, Elena Guerini-Rocco
OBJECTIVE: We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). MATERIALS AND METHODS: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test)...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28164427/application-of-circulating-tumor-dna-in-prospective-clinical-oncology-trials-standardization-of-preanalytical-conditions
#18
Lisanne F van Dessel, Nick Beije, Jean C A Helmijr, Silvia R Vitale, Jaco Kraan, Maxime P Look, Ronald de Wit, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens, Martijn P Lolkema
Circulating tumor DNA (ctDNA) has emerged as a potential new biomarker with diagnostic, predictive, and prognostic applications for various solid tumor types. Before beginning large prospective clinical trials to prove the added value of utilizing ctDNA in clinical practice, it is essential to investigate the effects of various preanalytical conditions on the quality of cell-free DNA (cfDNA) in general and of ctDNA in particular in order to optimize and standardize these conditions. Whole blood samples were collected from patients with metastatic cancer bearing a known somatic variant...
February 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28149760/comparison-of-methods-for-circulating-cell-free-dna-isolation-using-blood-from-cancer-patients-impact-on-biomarker-testing
#19
Clara Pérez-Barrios, Irene Nieto-Alcolado, María Torrente, Carolina Jiménez-Sánchez, Virginia Calvo, Lourdes Gutierrez-Sanz, Magda Palka, Encarnación Donoso-Navarro, Mariano Provencio, Atocha Romero
BACKGROUND: The implementation of liquid biopsy for biomarker testing and response to treatment monitoring in cancer patients would presumable increase laboratory throughput, requiring the development of automated methods for circulating free DNA (cfDNA) isolation. METHODS: The present study compares the MagNA Pure Compact (MPC) Nucleic Acid Isolation Kit I and Maxwell(®) RSC (MR) ccfDNA Plasma Kit and the later with QIAamp Circulating Nucleid Acid (QCNA) Kit using 57 plasma samples from cancer patients...
December 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28146051/circulating-cell-free-tumor-dna-detection-as-a-routine-tool-forlung-cancer-patient-management
#20
REVIEW
Julie A Vendrell, Frédéric Tran Mau-Them, Benoît Béganton, Sylvain Godreuil, Peter Coopman, Jérôme Solassol
Circulating tumoral DNA (ctDNA), commonly named "liquid biopsy", has emerged as a new promising noninvasive tool to detect biomarker in several cancers including lung cancer. Applications involving molecular analysis of ctDNA in lung cancer have increased and encompass diagnosis, response to treatment, acquired resistance and prognosis prediction, while bypassing the problem of tumor heterogeneity. ctDNA may then help perform dynamic genetic surveillance in the era of precision medicine through indirect tumoral genomic information determination...
January 29, 2017: International Journal of Molecular Sciences
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