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https://www.readbyqxmd.com/read/28102343/individualised-multiplexed-circulating-tumour-dna-assays-for-monitoring-of-tumour-presence-in-patients-after-colorectal-cancer-surgery
#1
Sarah B Ng, Clarinda Chua, Matthew Ng, Anna Gan, Polly Sy Poon, Melissa Teo, Cherylin Fu, Wei Qiang Leow, Kiat Hon Lim, Alexander Chung, Si-Lin Koo, Su Pin Choo, Danliang Ho, Steve Rozen, Patrick Tan, Mark Wong, William F Burkholder, Iain Beehuat Tan
Circulating tumour DNA (ctDNA) has the potential to be a specific biomarker for the monitoring of tumours in patients with colorectal cancer (CRC). Here, our aim was to develop a personalised surveillance strategy to monitor the clinical course of CRC after surgery. We developed patient-specific ctDNA assays based on multiplexed detection of somatic mutations identified from patient primary tumours, and applied them to detect ctDNA in 44 CRC patients, analysing a total of 260 plasma samples. We found that ctDNA detection correlated with clinical events - it is detectable in pre-operative but not post-operative plasma, and also in patients with recurrent CRC...
January 19, 2017: Scientific Reports
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/28075351/circulating-nucleosomes-and-nucleosome-modifications-as-biomarkers-in-cancer
#3
REVIEW
Peter McAnena, James A L Brown, Michael J Kerin
Traditionally the stratification of many cancers involves combining tumour and clinicopathological features (e.g., patient age; tumour size, grade, receptor status and location) to inform treatment options and predict recurrence risk and survival. However, current biomarkers often require invasive excision of the tumour for profiling, do not allow monitoring of the response to treatment and stratify patients into broad heterogeneous groups leading to inconsistent treatment responses. Here we explore and describe the benefits of using circulating biomarkers (nucleosomes and/or modifications to nucleosomes) as a non-invasive method for detecting cancer and monitoring response to treatment...
January 8, 2017: Cancers
https://www.readbyqxmd.com/read/28061772/use-of-liquid-biopsies-to-monitor-disease-progression-in-a-sarcoma-patient-a-case-report
#4
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/28060738/the-prognostic-value-of-clonal-heterogeneity-and-quantitative-assessment-of-plasma-circulating-clonal-ig-vdj-sequences-at-diagnosis-in-patients-with-follicular-lymphoma
#5
Clémentine Sarkozy, Sarah Huet, Victoria E H Carlton, Bettina Fabiani, Alain Delmer, Fabrice Jardin, Marie-Helene Delfau-Larue, Maya Hacini, Vincent Ribrag, Stéphanie Guidez, Malek Faham, Gilles Salles
Recent advances in next-generation sequencing (NGS) have enabled the quantitation of circulating tumour DNA (ctDNA) encoding the clonal rearranged V(D)J immunoglobulin locus. We aimed to evaluate the clonal heterogeneity of follicular lymphoma (FL) in the tumour and the plasma at diagnosis and to assess the prognostic value of the ctDNA level. Plasma samples at diagnosis were available for 34 patients registered in the PRIMA trial (NCT00140582). One tumour clonotype or more could be detected for 29 (85%) and 25 (74%) patients, respectively, in the tumour or plasma samples...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28007619/malignant-mesothelioma-biomarkers-from-discovery-to-use-in-clinical-practise-for-diagnosis-monitoring-screening-and-treatment
#6
REVIEW
Jenette Creaney, Bruce W S Robinson
Malignant pleural mesothelioma is a highly aggressive tumour associated with asbestos exposure. There are few effective treatment options for mesothelioma and patients have a very poor prognosis with a median survival of less than 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management and the search for a mesothelioma biomarker has been on-going for the past thirty years. Many traditional soluble (glyco)-protein biomarkers have been evaluated over this time and an ever increasing list of new biomarkers, including mRNA, DNA, miRNA and antibodies, are being reported from biomarker discovery projects...
December 19, 2016: Chest
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
#7
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/27999407/tumour-heterogeneity-the-key-advantages-of-single-cell-analysis
#8
REVIEW
Marta Tellez-Gabriel, Benjamin Ory, Francois Lamoureux, Marie-Francoise Heymann, Dominique Heymann
Tumour heterogeneity refers to the fact that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity), and it is caused by genetic and non-genetic factors. The heterogeneity of cancer cells introduces significant challenges in using molecular prognostic markers as well as for classifying patients that might benefit from specific therapies...
December 20, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27997533/exploratory-analysis-of-tp53-mutations-in-circulating-tumour-dna-as-biomarkers-of-treatment-response-for-patients-with-relapsed-high-grade-serous-ovarian-carcinoma-a-retrospective-study
#9
Christine A Parkinson, Davina Gale, Anna M Piskorz, Heather Biggs, Charlotte Hodgkin, Helen Addley, Sue Freeman, Penelope Moyle, Evis Sala, Karen Sayal, Karen Hosking, Ioannis Gounaris, Mercedes Jimenez-Linan, Helena M Earl, Wendi Qian, Nitzan Rosenfeld, James D Brenton
BACKGROUND: Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). METHODS AND FINDINGS: We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27994225/comparison-of-circulating-tumour-cells-and-circulating-cell-free-epstein-barr-virus-dna-in-patients-with-nasopharyngeal-carcinoma-undergoing-radiotherapy
#10
Jess Honganh Vo, Wen Long Nei, Min Hu, Wai Min Phyo, Fuqiang Wang, Kam Weng Fong, Terence Tan, Yoke Lim Soong, Shie Lee Cheah, Kiattisa Sommat, Huiyu Low, Belinda Ling, Johnson Ng, Wan Loo Tan, Kian Sing Chan, Lynette Oon, Jackie Y Ying, Min-Han Tan
Quantification of Epstein-Barr virus (EBV) cell-free DNA (cfDNA) is commonly used in clinical settings as a circulating biomarker in nasopharyngeal carcinoma (NPC), but there has been no comparison with circulating tumour cells (CTCs). Our study aims to compare the performance of CTC enumeration against EBV cfDNA quantitation through digital PCR (dPCR) and quantitative PCR. 74 plasma samples from 46 NPC patients at baseline and one month after radiotherapy with or without concurrent chemotherapy were analysed...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27983717/evaluation-of-methylation-biomarkers-for-detection-of-circulating-tumor-dna-and-application-to-colorectal-cancer
#11
Susan M Mitchell, Thu Ho, Glenn S Brown, Rohan T Baker, Melissa L Thomas, Aidan McEvoy, Zheng-Zhou Xu, Jason P Ross, Trevor J Lockett, Graeme P Young, Lawrence C LaPointe, Susanne K Pedersen, Peter L Molloy
Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA...
December 15, 2016: Genes
https://www.readbyqxmd.com/read/27959945/the-in-vitro-stability-of-circulating-tumour-dna
#12
Emanuela Henao Diaz, Jeffrey Yachnin, Henrik Grönberg, Johan Lindberg
OBJECTIVE: DNA from apoptotic cancer cells, present in the circulation, has the potential to facilitate genomic profiling and disease monitoring. However, only low fractions of total cell-free DNA originates from cancer cells, limiting the applicability of circulating tumour DNA (ctDNA). Optimal sample processing is consequently of uttermost importance. Therefore, we evaluated the in vitro stability of ctDNA. EXPERIMENTAL DESIGN: Blood was collected in 10 ml EDTA or Streck tubes...
2016: PloS One
https://www.readbyqxmd.com/read/27933110/profiling-lung-adenocarcinoma-by-liquid-biopsy-can-one-size-fit-all
#13
Harry W Clifford, Amy P Cassidy, Courtney Vaughn, Evaline S Tsai, Bianka Seres, Nirmesh Patel, Hannah L O'Neill, Emil Hewage, John W Cassidy
BACKGROUND: Cancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minimally invasive liquid biopsies can give temporal resolution to a tumour's genetic profile and allow the monitoring of treatment response through levels of circulating tumour DNA (ctDNA). However, the detection of ctDNA in repeated liquid biopsies is currently limited by economic and time constraints associated with targeted sequencing...
2016: Cancer Nanotechnology
https://www.readbyqxmd.com/read/27929064/acquired-ras-or-egfr-mutations-and-duration-of-response-to-egfr-blockade-in-colorectal-cancer
#14
Beth O Van Emburgh, Sabrina Arena, Giulia Siravegna, Luca Lazzari, Giovanni Crisafulli, Giorgio Corti, Benedetta Mussolin, Federica Baldi, Michela Buscarino, Alice Bartolini, Emanuele Valtorta, Joana Vidal, Beatriz Bellosillo, Giovanni Germano, Filippo Pietrantonio, Agostino Ponzetti, Joan Albanell, Salvatore Siena, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Clara Montagut, Alberto Bardelli
Blockade of the epidermal growth factor receptor (EGFR) with the monoclonal antibodies cetuximab or panitumumab is effective in a subset of colorectal cancers (CRCs), but the emergence of resistance limits the efficacy of these therapeutic agents. At relapse, the majority of patients develop RAS mutations, while a subset acquires EGFR extracellular domain (ECD) mutations. Here we find that patients who experience greater and longer responses to EGFR blockade preferentially develop EGFR ECD mutations, while RAS mutations emerge more frequently in patients with smaller tumour shrinkage and shorter progression-free survival...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27917295/circulating-human-papillomavirus-dna-detected-using-droplet-digital-pcr-in-the-serum-of-patients-diagnosed-with-early-stage-human-papillomavirus-associated-invasive-carcinoma
#15
Emmanuelle Jeannot, Véronique Becette, Maura Campitelli, Marie-Ange Calméjane, Emmanuelle Lappartient, Evelyne Ruff, Stéphanie Saada, Allyson Holmes, Dominique Bellet, Xavier Sastre-Garau
Specific human papillomavirus genotypes are associated with most ano-genital carcinomas and a large subset of oro-pharyngeal carcinomas. Human papillomavirus DNA is thus a tumour marker that can be detected in the blood of patients for clinical monitoring. However, data concerning circulating human papillomavirus DNA in cervical cancer patients has provided little clinical value, due to insufficient sensitivity of the assays used for the detection of small sized tumours. Here we took advantage of the sensitive droplet digital PCR method to identify circulating human papillomavirus DNA in patients with human papillomavirus-associated carcinomas...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27903276/accurate-prediction-of-response-to-endocrine-therapy-in-breast-cancer-patients-current-and-future-biomarkers
#16
REVIEW
Cigdem Selli, J Michael Dixon, Andrew H Sims
Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells...
December 1, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27899805/circulating-tumour-dna-analysis-demonstrates-spatial-mutational-heterogeneity-that-coincides-with-disease-relapse-in-myeloma
#17
S Mithraprabhu, T Khong, M Ramachandran, A Chow, D Klarica, L Mai, S Walsh, D Broemeling, A Marziali, M Wiggin, J Hocking, A Kalff, B Durie, A Spencer
Mutational characterisation in multiple myeloma (MM) currently relies on bone marrow (BM) biopsy, which fails to capture the putative spatial and genetic heterogeneity of this multifocal disease. Analysis of plasma (PL)-derived circulating free tumour DNA (ctDNA) as an adjunct to BM biopsy, for mutational characterisation and tracking disease progression, was evaluated. Paired BM MM cell DNA and ctDNA from 33 relapsed/refractory (RR) and 15 newly diagnosed (ND) patients were analysed for KRAS, NRAS, BRAF and TP53 mutations using the OnTarget Mutation Detection (OMD) platform...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27866095/continuing-egfr-inhibition-beyond-progression-in-advanced-non-small-cell-lung-cancer
#18
REVIEW
Timothy A Yap, Aislinn Macklin-Doherty, Sanjay Popat
The majority of patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) respond to first-line EGFR tyrosine kinase inhibitors (TKIs), but nearly all inevitably acquire resistance and develop disease progression. Conventional practice would be to switch treatments to second-line therapy. However, continuing TKIs beyond progression is becoming increasingly commonplace in patients with indolent, small volume asymptomatic growth, who may potentially continue to derive ongoing clinical benefit and to avoid a 'withdrawal tumour flare'...
January 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/27864864/genetics-of-adrenocortical-tumours
#19
T Åkerström, T Carling, F Beuschlein, P Hellman
The recently available genomic sequencing techniques have led to breakthroughs in understanding of the underlying genetic mechanisms in adrenocortical tumours. Disease-causing mutations have been described for aldosterone-producing adenomas, cortisol-producing adenomas and adrenocortical carcinomas. Further, knowledge gained from transcriptome analyses and methylation arrays has provided new insights into the development of these tumours. Elucidation of the genomic landscape of adrenocortical tumours and improved techniques may in the future be useful for early diagnosis through the detection of mutated DNA in the circulation...
December 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27753035/digital-pcr-of-genomic-rearrangements-for-monitoring-circulating-tumour-dna
#20
Hongdo Do, Daniel Cameron, Ramyar Molania, Bibhusal Thapa, Gareth Rivalland, Paul L Mitchell, Carmel Murone, Thomas John, Anthony Papenfuss, Alexander Dobrovic
Identifying circulating tumour DNA (ctDNA) for monitoring of cancer therapy is dependent on the development of readily designed, sensitive cancer-specific DNA markers. Genomic rearrangements that are present in the vast majority of cancers provide such markers.Tumour DNA isolated from two fresh-frozen lung tumours underwent whole genome sequencing. Genomic rearrangements were detected using a new computational algorithm, GRIDSS. Four genomic rearrangements from each tumour were chosen for further study using rearrangement-specific primers...
2016: Advances in Experimental Medicine and Biology
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