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circulating tumour DNA

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https://www.readbyqxmd.com/read/29113230/squamous-cell-transformation-and-egfr-t790m-mutation-as-acquired-resistance-mechanisms-in-a-patient-with-lung-adenocarcinoma-treated-with-a-tyrosine-kinase-inhibitor-a-case-report
#1
Rossella Bruno, Agnese Proietti, Greta Alì, Gianfranco Puppo, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini
The present case report describes the infrequent coexistence of squamous cell transformation and the epidermal growth factor receptor (EGFR) T790M mutation as resistance mechanisms to first line treatment with tyrosine kinase inhibitors. The patient was a 44-year-old female, diagnosed with a primitive advanced lung adenocarcinoma with bone metastases. The tumor was positive for the EGFR exon 19 deletion, therefore the patient was treated with afatinib (40 mg/day, orally) and radiotherapy for bone lesions. After 16 months, the patient developed resistance...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29110846/egfr-mutation-prevalence-in-asia-pacific-and-russian-patients-with-advanced-nsclc-of-adenocarcinoma-and-non-adenocarcinoma-histology-the-ignite-study
#2
Baohui Han, Sergei Tjulandin, Koichi Hagiwara, Nicola Normanno, Laksmi Wulandari, Konstantin Laktionov, Achmad Hudoyo, Yong He, Yi-Ping Zhang, Meng-Zhao Wang, Chien Ying Liu, Marianne Ratcliffe, Rose McCormack, Martin Reck
OBJECTIVES: Limited understanding exists of epidermal growth factor receptor (EGFR) mutation frequency in less common subgroups of advanced non-small-cell lung cancer (aNSCLC) (e.g. squamous cell carcinoma [SCC]), and to what extent local practices exclude patients from EGFR testing based on their clinical characteristics. MATERIALS AND METHODS: IGNITE (non-comparative/-interventional; NCT01788163) was conducted in 90 centres (Asia-Pacific/Russia). Eligible patients: local/metastatic aNSCLC; chemotherapy-naïve, newly-diagnosed/recurrent disease after resection; ineligible for curative treatment...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29078173/very-early-response-of-circulating-tumour-derived-dna-in-plasma-predicts-efficacy-of-nivolumab-treatment-in-patients-with-non-small-cell-lung-cancer
#3
Yuki Iijima, Yosuke Hirotsu, Kenji Amemiya, Yoshihiko Ooka, Hitoshi Mochizuki, Toshio Oyama, Takahiro Nakagomi, Yoshinori Uchida, Yoichi Kobayashi, Toshiharu Tsutsui, Yumiko Kakizaki, Taichiro Goto, Yoshihiro Miyashita, Masao Omata
INTRODUCTION: Immunotherapy has become a treatment option for lung cancer. The utility of nivolumab as second-line treatment for non-small cell lung cancer has been proven, but predictive biomarkers influencing its efficacy remain unknown. METHODS: This study involved 14 patients who were treated with nivolumab from February 1 to September 30, 2016. The early response of the level of circulating tumour DNA (ctDNA) after starting nivolumab was evaluated to ascertain whether it could predict treatment outcome...
October 24, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29072078/integrated-multifunctional-electrochemistry-microchip-for-highly-efficient-capture-release-lysis-and-analysis-of-circulating-tumor-cells
#4
Shuangqian Yan, Peng Chen, Xuemei Zeng, Xian Zhang, Yiwei Li, Yun Xia, Jie Wang, Xiaofang Dai, Xiaojun Feng, Wei Du, Bi-Feng Liu
The circulating tumor cells (CTCs) in the blood allow the noninvasive analysis of metastatic mechanisms, cancer diagnosis, prognosis, disease monitoring, and precise therapy through "liquid biopsies". However, there is no integrated and robust multifunctional microchip, which not only could highly efficient capture CTCs, but also fast release and lyse cells on one single chip without using other biochemical agents for downstream biomedical analysis. In this work, we integrated the three functions in one electrochemical microchip (echip) by intentionally designing a cactus-like, topologically structured conductive array consisted of a PDMS micropillar-array core and an electroconductive gold coating layer with hierarchical structure...
November 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29069768/direct-comparison-study-of-dna-methylation-markers-in-epcam-positive-circulating-tumour-cells-corresponding-circulating-tumour-dna-and-paired-primary-tumours-in-breast-cancer
#5
Maria Chimonidou, Areti Strati, Nikos Malamos, Sophia Kouneli, Vassilis Georgoulias, Evi Lianidou
Circulating Tumour Cells (CTCs) and circulating tumour DNA (ctDNA) represent a non-invasive liquid biopsy approach for the follow-up and therapy management of cancer patients. We evaluated whether DNA methylation status in CTCs and ctDNA is comparable and whether it reflects the status of primary tumours. We compared the methylation status of three genes, SOX17, CST6 and BRMS1 in primary tumours, corresponding CTCs and ctDNA in 153 breast cancer patients and healthy individuals, by using real time methylation specific PCR...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29067216/genotyping-tumour-dna-in-cerebrospinal-fluid-and-plasma-of-a-her2-positive-breast-cancer-patient-with-brain-metastases
#6
Giulia Siravegna, Elena Geuna, Benedetta Mussolin, Giovanni Crisafulli, Alice Bartolini, Danilo Galizia, Laura Casorzo, Ivana Sarotto, Maurizio Scaltriti, Anna Sapino, Alberto Bardelli, Filippo Montemurro
BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment...
2017: ESMO Open
https://www.readbyqxmd.com/read/29061138/the-evidence-base-for-circulating-tumour-dna-blood-based-biomarkers-for-the-early-detection-of-cancer-a-systematic-mapping-review
#7
Ian A Cree, Lesley Uttley, Helen Buckley Woods, Hugh Kikuchi, Anne Reiman, Susan Harnan, Becky L Whiteman, Sian Taylor Philips, Michael Messenger, Angela Cox, Dawn Teare, Orla Sheils, Jacqui Shaw
BACKGROUND: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest...
October 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29057681/liquid-biopsy-in-non-small-cell-lung-cancer-a-key-role-in-the-future-of-personalized-medicine
#8
Can Pi, Ming-Feng Zhang, Xiao-Xiao Peng, Yi-Chen Zhang, Chong-Rui Xu, Qing Zhou
Liquid biopsies, especially the analysis of circulating tumor DNA (ctDNA), as a novel and non-invasive method for the diagnosis and monitoring of non-small cell lung cancer (NSCLC) have already been implemented in clinical settings. The majority of ctDNA is released from apoptotic or necrotic tumor cells, thus reflecting the genetic profile of a tumor. Numerous studies have reported a high concordance in mutation profiles derived from liquid biopsy and tissue biopsy, especially in driver genes. Liquid biopsy could overcome the clonal heterogeneity of tumour biopsy, as it provides a single snapshot of a tumour tissue...
November 14, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29050295/a-comprehensive-study-of-circulating-tumour-cells-at-the-moment-of-prostate-cancer-diagnosis-biological-and-clinical-implications-of-egfr-ar-and-snps
#9
Ignacio Puche-Sanz, María J Alvarez-Cubero, Manrique Pascual-Geler, Alba Rodríguez-Martínez, Miguel Delgado-Rodríguez, José L García-Puche, José Expósito, Inmaculada Robles-Fernández, Carmen Entrala-Bernal, José A Lorente, José M Cózar-Olmo, María J Serrano
Circulating tumor cells (CTCs) have been recently accepted as prognostic markers in metastatic prostate cancer (PCa). However, very few studies have analyzed their role in early-stage PCa. The aim of this research is to study the value of CTCs at the moment of PCa diagnosis and to identify different subpopulations of CTCs. Patients with PSA value > 4 ng/ml and clinical suspicion of PCa were included. Samples were collected immediately before prostatic biopsy. CTCs were isolated by immunomagnetic technique using a multi-CK specific antibody...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045530/tracking-evolution-of-aromatase-inhibitor-resistance-with-circulating-tumour-dna-analysis-in-metastatic-breast-cancer
#10
Charlotte Fribbens, Isaac Garcia Murillas, Matthew Beaney, Sarah Hrebien, Ben O'Leary, Lucy Kilburn, Karen Howarth, Michael Epstein, Emma Green, Nitzan Rosenfeld, Alistair Ring, Stephen Johnston, Nicholas Turner
Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Patients and Methods: 83 patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study...
October 4, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29035356/circulating-tumour-dna-methylation-markers-for-diagnosis-and-prognosis-of-hepatocellular-carcinoma
#11
Rui-Hua Xu, Wei Wei, Michal Krawczyk, Wenqiu Wang, Huiyan Luo, Ken Flagg, Shaohua Yi, William Shi, Qingli Quan, Kang Li, Lianghong Zheng, Heng Zhang, Bennett A Caughey, Qi Zhao, Jiayi Hou, Runze Zhang, Yanxin Xu, Huimin Cai, Gen Li, Rui Hou, Zheng Zhong, Danni Lin, Xin Fu, Jie Zhu, Yaou Duan, Meixing Yu, Binwu Ying, Wengeng Zhang, Juan Wang, Edward Zhang, Charlotte Zhang, Oulan Li, Rongping Guo, Hannah Carter, Jian-Kang Zhu, Xiaoke Hao, Kang Zhang
An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive 'liquid biopsy' for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated...
October 9, 2017: Nature Materials
https://www.readbyqxmd.com/read/28982739/discovery-of-methylated-circulating-dna-biomarkers-for-comprehensive-non-invasive-monitoring-of-treatment-response-in-metastatic-colorectal-cancer
#12
Ludovic Barault, Alessio Amatu, Giulia Siravegna, Agostino Ponzetti, Sebastian Moran, Andrea Cassingena, Benedetta Mussolin, Chiara Falcomatà, Alexandra M Binder, Carmen Cristiano, Daniele Oddo, Simonetta Guarrera, Carlotta Cancelliere, Sara Bustreo, Katia Bencardino, Sean Maden, Alice Vanzati, Patrizia Zavattari, Giuseppe Matullo, Mauro Truini, William M Grady, Patrizia Racca, Karin B Michels, Salvatore Siena, Manel Esteller, Alberto Bardelli, Andrea Sartore-Bianchi, Federica Di Nicolantonio
OBJECTIVE: Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC)...
October 5, 2017: Gut
https://www.readbyqxmd.com/read/28958829/monitoring-treatment-response-and-metastatic-relapse-in-advanced-bladder-cancer-by-liquid-biopsy-analysis
#13
Karin Birkenkamp-Demtröder, Emil Christensen, Iver Nordentoft, Michael Knudsen, Ann Taber, Søren Høyer, Philippe Lamy, Mads Agerbæk, Jørgen Bjerggaard Jensen, Lars Dyrskjøt
Of the patients undergoing radical cystectomy, 20-80% experience relapse. Minimally invasive methods for early detection of metastatic relapse after cystectomy and for monitoring ongoing therapy are urgently needed to improve individualised follow-up and treatment. Therefore, we evaluated the use of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84 personalised digital droplet polymerase chain reaction assays targeting 61 genes...
September 25, 2017: European Urology
https://www.readbyqxmd.com/read/28864095/minimal-residual-disease-in-chronic-lymphocytic-leukaemia
#14
REVIEW
José Antonio García Vela, José Antonio García Marco
Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing. A therapeutic approach guided by the level of MRD might also determine which patients would benefit from an early stop or consolidation therapy...
August 29, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28845132/cell-free-dna-in-non-small-cell-lung-cancer
#15
Vaida Gedvilaitė, Diana Schveigert, Saulius Cicėnas
Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). Advances in the knowledge of the biology of non-small cell lung cancer have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients' overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic...
2017: Acta medica Lituanica
https://www.readbyqxmd.com/read/28843359/combination-osimertinib-and-gefitinib-in-c797s-and-t790m-egfr-mutated-non-small-cell-lung-cancer
#16
Surein Arulananda, Hongdo Do, Ashan Musafer, Paul Mitchell, Alexander Dobrovic, Thomas John
INTRODUCTION: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor has demonstrated efficacy in tumors harboring the EGFR T790M resistance mutation. Inevitably, resistance to third-generation inhibitors results in disease progression, with the EGFR C797S mutation being one of several resistance pathways identified to date. On the basis of preclinical data, we report what is the first known case of a patient harboring the T790M and C797S mutations in trans treated with combination gefitinib and osimertinib...
November 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28841569/results-of-the-first-external-quality-assessment-scheme-eqa-for-isolation-and-analysis-of-circulating-tumour-dna-ctdna
#17
Verena Haselmann, Parviz Ahmad-Nejad, Wolf J Geilenkeuser, Angelika Duda, Merle Gabor, Romy Eichner, Simon Patton, Michael Neumaier
BACKGROUND: Circulating tumour DNA (ctDNA) is considered to have a high potential for future management of malignancies. This pilot external quality assessment (EQA) scheme aimed to address issues of analytical quality in this new area of laboratory diagnostics. METHODS: The EQA scheme consisted of three 2-mL EDTA-plasma samples spiked with fragmented genomic DNA with a mutant allele frequency ranging from 0% to 10% dedicated to the analysis of nine known sequence variations in KRAS codon 12/13 and of BRAF V600E...
August 25, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28827745/establishing-pnb-qpcr-for-quantifying-minimal-ctdna-concentrations-during-tumour-resection
#18
T Ehlert, S Tug, A Brahmer, V Neef, F Heid, C Werner, B Jansen-Winkeln, W Kneist, H Lang, I Gockel, P Simon
The analysis of blood plasma or serum as a non-invasive alternative to tissue biopsies is a much-pursued goal in cancer research. Various methods and approaches have been presented to determine a patient's tumour status, chances of survival, and response to therapy from serum or plasma samples. We established PNB-qPCR (Pooled, Nested, WT-Blocking qPCR), a highly specific nested qPCR with various modifications to detect and quantify minute amounts of circulating tumour DNA (ctDNA) from very limited blood plasma samples...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28809864/predicting-response-to-radical-chemo-radiotherapy-with-circulating-hpv-dna-in-locally-advanced-head-and-neck-squamous-carcinoma
#19
Jen Y Lee, Isaac Garcia-Murillas, Rosalind J Cutts, David Gonzalez De Castro, Lorna Grove, Tara Hurley, Fuqiang Wang, Christopher Nutting, Katie Newbold, Kevin Harrington, Nicholas Turner, Shreerang Bhide
BACKGROUND: Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT, which causes significant morbidity. We assessed the role of circulating HPV DNA in identifying 'true' residual disease. METHODS: We prospectively recruited test (n=55) and validation (n=33) cohorts. HPV status was confirmed by E7 RT-PCR...
September 5, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28790338/statistical-analysis-of-mutant-allele-frequency-level-of-circulating-cell-free-dna-and-blood-cells-in-healthy-individuals
#20
Ligang Xia, Zhoufang Li, Bo Zhou, Geng Tian, Lidong Zeng, Hongyu Dai, Xiaohua Li, Chaoyu Liu, Shixin Lu, Feiyue Xu, Xiaonian Tu, Fang Deng, Yuancai Xie, Weiren Huang, Jiankui He
Cell-free DNA (cfDNA) in plasma has emerged as a potential important biomarker in clinical diagnostics, particularly in cancer. However, somatic mutations are also commonly found in healthy individuals, which interfere with the effectiveness for cancer diagnostics. This study examined the background somatic mutations in white blood cells (WBC) and cfDNA in healthy controls based on sequencing data from 821 non-cancer individuals and several cancer samples with the aim of understanding the patterns of mutations detected in cfDNA...
August 8, 2017: Scientific Reports
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