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Cell free circulating cancer DNA

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https://www.readbyqxmd.com/read/28101802/cold-pcr-technologies-in-the-area-of-personalized-medicine-methodology-and-applications
#1
REVIEW
Florence Mauger, Alexandre How-Kit, Jörg Tost
Somatic mutations bear great promise for use as biomarkers for personalized medicine, but are often present only in low abundance in biological material and are therefore difficult to detect. Many assays for mutation analysis in cancer-related genes (hotspots) have been developed to improve diagnosis, prognosis, prediction of drug resistance, and monitoring of the response to treatment. Two major approaches have been developed: mutation-specific amplification methods and methods that enrich and detect mutations without prior knowledge on the exact location and identity of the mutation...
January 18, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28096542/liquid-biopsy-in-2016-circulating-tumour-cells-and-cell-free-dna-in-gastrointestinal-cancer
#2
Klaus Pantel, Catherine Alix-Panabières
No abstract text is available yet for this article.
January 18, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28081183/circulating-cell-free-dna-in-dogs-with-mammary-tumors-short-and-long-fragments-and-integrity-index
#3
Giorgia Beffagna, Alessandro Sammarco, Chiara Bedin, Chiara Romualdi, Marta Mainenti, Antonio Mollo, Laura Cavicchioli, Silvia Ferro, Davide Trez, Raffaella De Maria, Donato Nitti, Andrea Saccani, Michelangelo Campanella, Marco Agostini, Valentina Zappulli
Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs...
2017: PloS One
https://www.readbyqxmd.com/read/28063009/dna-methylation-signatures-in-circulating-cell-free-dna-as-biomarkers-for-the-early-detection-of-cancer
#4
REVIEW
Junyun Wang, Xiao Han, Yingli Sun
Detecting cell-free DNA (cfDNA) or circulating tumor DNA (ctDNA) in plasma or serum could serve as a "liquid biopsy", which would be useful for numerous diagnostic applications. cfDNA methylation detection is one of the most promising approaches for cancer risk assessment. Here, we reviewed the literature related to the use of serum or plasma circulating cell-free DNA for cancer diagnosis in the early stage and their power as future biomarkers.
January 5, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28061772/use-of-liquid-biopsies-to-monitor-disease-progression-in-a-sarcoma-patient-a-case-report
#5
Heidi M Namløs, Olga Zaikova, Bodil Bjerkehagen, Daniel Vodák, Eivind Hovig, Ola Myklebost, Kjetil Boye, Leonardo A Meza-Zepeda
BACKGROUND: Many patients experience local recurrence or metastases after receiving potentially curative treatment, and early detection of these events is important for disease control. Recent technological advances make it possible to use blood plasma containing circulating cell-free tumour DNA (ctDNA) as a liquid biopsy. In this case report we show how serial liquid biopsies can be used to monitor the disease course and detect disease recurrence in a sarcoma patient. CASE PRESENTATION: A 55-year-old male presented with a rapidly growing, painful palpable mass in the left groin region, and a biopsy revealed a high-grade malignant spindle cell sarcoma...
January 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28061461/estimation-of-cell-free-circulating-egfr-mutation-concentration-predicts-outcomes-in-nsclc-patients-treated-with-egfr-tkis
#6
Yan-Juan Zhu, Hai-Bo Zhang, Yi-Hong Liu, Fu-Li Zhang, Ya-Zhen Zhu, Yong Li, Jian-Ping Bai, Li-Rong Liu, Yan-Chun Qu, Xin Qu, Xian Chen, Yan Li, Guang-Juan Zheng
Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060757/line-1-hypomethylation-status-of-circulating-cell-free-dna-in-plasma-as-a-biomarker-for-colorectal-cancer
#7
Yuzo Nagai, Eiji Sunami, Yoko Yamamoto, Keisuke Hata, Satoshi Okada, Koji Murono, Koji Yasuda, Kensuke Otani, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Hiroaki Nozawa, Soichiro Ishihara, Dave S B Hoon, Toshiaki Watanabe
Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC. LINE-1 hypomethylation level in plasma cfDNA in 114 CRC patients was retrospectively examined by absolute quantitative analysis of methylated alleles real-time PCR, and was expressed using LINE-1 hypomethylation index (LHI) [unmethylated copy number/ (methylated copy number + unmethylated copy number)]...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28056336/the-clinical-role-of-circulating-free-tumor-dna-in-gastrointestinal-malignancy
#8
REVIEW
Jessica A Howell, Shahid A Khan, Susanne Knapp, Mark R Thursz, Rohini Sharma
Circulating cell-free DNA (cfDNA) is DNA released from necrotic or apoptotic cells into the bloodstream. While both healthy cells and cancer cells release cfDNA, tumors are associated with higher levels of tumor-derived circulating cell-free DNA (ctDNA) detectable in blood. Absolute levels of ctDNA and its genetic mutations and epigenetic changes show promise as potentially useful biomarkers of tumor biology, progression, and response to therapy. Moreover, studies have demonstrated the discriminative accuracy of ctDNA levels for diagnosis of gastrointestinal cancer compared with benign inflammatory diseases...
December 22, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28035318/circulating-biomarkers-in-bladder-cancer
#9
REVIEW
Lakshminarayanan Nandagopal, Guru Sonpavde
Bladder cancer is a molecularly heterogeneous disease characterized by multiple unmet needs in the realm of diagnosis, clinical staging, monitoring and therapy. There is an urgent need to develop precision medicine for advanced urothelial carcinoma. Given the difficulty of serial analyses of metastatic tumor tissue to identify resistance and new therapeutic targets, development of non-invasive monitoring using circulating molecular biomarkers is critically important. Although the development of circulating biomarkers for the management of bladder cancer is in its infancy and may currently suffer from lower sensitivity of detection, they have inherent advantages owing to non-invasiveness...
October 27, 2016: Bladder Cancer
https://www.readbyqxmd.com/read/28034880/polyclonal-secondary-fgfr2-mutations-drive-acquired-resistance-to-fgfr-inhibition-in-patients-with-fgfr2-fusion-positive-cholangiocarcinoma
#10
Lipika Goyal, Supriya K Saha, Leah Y Liu, Giulia Siravegna, Ignaty Leshchiner, Leanne G Ahronian, Jochen K Lennerz, Phuong Vu, Vikram Deshpande, Avinash Kambadakone, Benedetta Mussolin, Stephanie Reyes, Laura Henderson, Jiaoyuan Elisabeth Sun, Emily E Van Seventer, Joseph M Gurski, Sabrina Baltschukat, Barbara Schacher-Engstler, Louise Barys, Christelle Stamm, Pascal Furet, David P Ryan, James R Stone, A John Iafrate, Gad Getz, Diana Graus Porta, Ralph Tiedt, Alberto Bardelli, Dejan Juric, Ryan B Corcoran, Nabeel Bardeesy, Andrew X Zhu
Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases...
December 29, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28031532/cell-free-methylation-markers-with-diagnostic-and-prognostic-potential-in-hepatocellular-carcinoma
#11
Chang-Yi Lu, Shih-Ya Chen, Hui-Ling Peng, Pu-Yeh Kan, Wan-Chi Chang, Chia-Jui Yen
Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality. There is a dearth of effective early diagnostic tools, so liver resection surgery and liver transplantation are the only effective medical treatments. The most commonly used marker for HCC detection is serum alpha fetoprotein (AFP), which has low sensitivity and specificity. Because aberrant DNA methylation of genes and miRNAs occurs early in most cancers, we explored whether circulating methylation markers could be promising clinical tools for HCC diagnosis...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029553/somatic-mutation-detection-using-various-targeted-detection-assays-in-paired-samples-of-circulating-tumor-dna-primary-tumor-and-metastases-from-patients-undergoing-resection-of-colorectal-liver-metastases
#12
Nick Beije, Jean C Helmijr, Marjolein J A Weerts, Corine M Beaufort, Matthew Wiggin, Andre Marziali, Cornelis Verhoef, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR)...
October 10, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28027313/base-position-error-rate-analysis-of-next-generation-sequencing-applied-to-circulating-tumor-dna-in-non-small-cell-lung-cancer-a-prospective-study
#13
Nicolas Pécuchet, Eleonora Zonta, Audrey Didelot, Pierre Combe, Constance Thibault, Laure Gibault, Camille Lours, Yves Rozenholc, Valérie Taly, Pierre Laurent-Puig, Hélène Blons, Elizabeth Fabre
BACKGROUND: Circulating tumor DNA (ctDNA) is an approved noninvasive biomarker to test for the presence of EGFR mutations at diagnosis or recurrence of lung cancer. However, studies evaluating ctDNA as a noninvasive "real-time" biomarker to provide prognostic and predictive information in treatment monitoring have given inconsistent results, mainly due to methodological differences. We have recently validated a next-generation sequencing (NGS) approach to detect ctDNA. Using this new approach, we evaluated the clinical usefulness of ctDNA monitoring in a prospective observational series of patients with non-small cell lung cancer (NSCLC)...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/28027295/blood-based-analysis-of-circulating-cell-free-dna-and-tumor-cells-for-early-cancer-detection
#14
Klaus Pantel
In a Perspective, Klaus Pantel discusses prospects for use of cell-free DNA and circulating tumor cells in cancer detection.
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/28010185/methodological-biological-and-clinical-aspects-of-circulating-free-dna-in-metastatic-colorectal-cancer
#15
REVIEW
Karen-Lise G Spindler
BACKGROUND: Circulating DNA can be used to measure the total cell-free DNA (cfDNA) and for detection and quantification of tumor-specific genetic alterations in the peripheral blood, and the broad clinical potential of circulating DNA has attracted increasing focus over the past decade. Concentrations of circulating DNA are high in metastatic colorectal cancer (CRC), and the total levels of cfDNA have been reported to hold strong prognostic value. Colorectal tumors are characterized by a high frequency of well known, clinically relevant genetic alteration, which is readily detected in the cfDNA and holds potential for tailoring of palliative therapy and for monitoring during treatment...
January 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28006816/egfr-mutation-detection-in-circulating-cell-free-dna-of-lung-adenocarcinoma-patients-analysis-of-lux-lung-3-and-6
#16
Yi-Long Wu, Lecia V Sequist, Cheng-Ping Hu, Jifeng Feng, Shun Lu, Yunchao Huang, Wei Li, Mei Hou, Martin Schuler, Tony Mok, Nobuyuki Yamamoto, Kenneth O'Byrne, Vera Hirsh, Neil Gibson, Dan Massey, Miyoung Kim, James Chih-Hsin Yang
BACKGROUND: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). METHODS: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit...
January 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28004119/yttrium-90-radioembolization-for-colorectal-cancer-liver-metastases-in-kras-wild-type-and-mutant-patients-clinical-and-ccfdna-studies
#17
E Janowski, O Timofeeva, S Chasovskikh, M Goldberg, A Kim, F Banovac, D Pang, A Dritschilo, K Unger
Patients with unresectable, chemo-refractory colorectal cancer liver metastases (CRCLM) have limited local treatment options. We report our institutional experience on the efficacy of resin-based yttrium-90 (90Y) radioembolization for the treatment of CRCLM and our findings on associated circulating cell-free DNA (ccfDNA) studies. A total of 58 patients treated with 90Y for CRCLM at the Medstar Georgetown University Hospital had a median survival of 6 months [95% confidence interval (CI), 4.55‑7.45 months] after treatment, with a 12-month survival rate of 33%...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/28002980/targeting-the-egfr-t790m-mutation-in-non-small-cell-lung-cancer
#18
Nicola Normanno, Monica Rosaria Maiello, Nicoletta Chicchinelli, Alessia Iannaccone, Claudia Esposito, Rossella De Cecio, Amelia D'alessio, Antonella De Luca
The presence of activating mutations of the epidermal growth factor receptor (EGFR) is predictive of response to first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). However, patients that initially respond to these drugs inexorably become resistant. The T790M mutation in the exon 20 of the EGFR is the main mechanism of resistance to EGFR TKIs occurring in over 50% of the cases. Third generation EGFR TKIs have been shown to be active in patients who progressed after TKI treatment and carry the T790M mutation...
December 23, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27999323/circulating-cell-free-dna-levels-could-predict-oncological-outcomes-of-patients-undergoing-esophagectomy-for-esophageal-squamous-cell-carcinoma
#19
Chih-Cheng Hsieh, Han-Shui Hsu, Shih-Ching Chang, Yann-Jang Chen
Circulating cell-free DNA (cfDNA) is a potential biomarker for cancer progression but its role is unclear in patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. We investigated relationships between plasma cfDNA levels and clinicopathological parameters in ESCC patients. Eighty-one ESCC patients who received esophagectomy were enrolled. Plasma samples from these patients and 95 normal controls were collected. DNA copy numbers were measured by real-time quantitative PCR. Subjects were divided into two groups by cfDNA level...
December 17, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27993161/circulating-cell-free-dna-based-epigenetic-assay-can-detect-early-breast-cancer
#20
Natsue Uehiro, Fumiaki Sato, Fengling Pu, Sunao Tanaka, Masahiro Kawashima, Kosuke Kawaguchi, Masahiro Sugimoto, Shigehira Saji, Masakazu Toi
BACKGROUND: Circulating cell-free DNA (cfDNA) has recently been recognized as a resource for biomarkers of cancer progression, treatment response, and drug resistance. However, few have demonstrated the usefulness of cfDNA for early detection of cancer. Although aberrant DNA methylation in cfDNA has been reported for more than a decade, its diagnostic accuracy remains unsatisfactory for cancer screening. Thus, the aim of the present study was to develop a highly sensitive cfDNA-based system for detection of primary breast cancer (BC) using epigenetic biomarkers and digital PCR technology...
December 19, 2016: Breast Cancer Research: BCR
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