Abstract:
BACKGROUND:When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use in ultra-deep sequencing to identify such mutations in cfDNA. METHODS:Our panel ('SiRe') covers 568 mutations in six genes (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα)involved in non-small-cell lung cancer (NSCLC), gastrointestinal stromal tumour, colorectal carcinoma and melanoma. We evaluated the panel performance in three steps. First, we analysed its analytical sensitivity on cell line DNA and by using an artificial reference standard with multiple mutations in different genes. Second, we analysed cfDNA from cancer patients at presentation (n=42), treatment response (n=12) and tumour progression (n=11); all patients had paired tumour tissue and cfDNA previously genotyped with a Taqman-derived assay (TDA). Third, we tested blood samples prospectively collected from NSCLC patients (n=79) to assess the performance of SiRe in clinical practice. RESULTS:SiRe had a high analytical performance and a 0.01% lower limit of detection. In the retrospective series, SiRe detected 40 EGFR, 11 KRAS, 1 NRAS and 5 BRAF mutations (96.8% concordance with TDA). In the baseline samples, SiRe had 100% specificity and 79% sensitivity relative to tumour tissue. Finally, in the prospective series, SiRe detected 8.7% (4/46) of EGFR mutations at baseline and 42.9% (9/21) of EGFR p.T790M in patients at tumour progression. CONCLUSIONS:SiRe is a feasible NGS panel for cfDNA analysis in clinical practice.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Malapelle U,Mayo de-Las-Casas C,Rocco D,Garzon M,Pisapia P,Jordana-Ariza N,Russo M,Sgariglia R,De Luca C,Pepe F,Martinez-Bueno A,Morales-Espinosa D,González-Cao M,Karachaliou N,Viteri Ramirez S,Bellevicine C,Molina-Vila Mdoi
10.1038/bjc.2017.8subject
Has Abstractpub_date
2017-03-14 00:00:00pages
802-810issue
6eissn
0007-0920issn
1532-1827pii
bjc20178journal_volume
116pub_type
杂志文章abstract::Rhizoxin is a tubulin-binding anti-neoplastic agent which is active in a range of murine tumour models. The recommended schedule, of intravenous (i.v.) bolus administration at a dose of 2 mg m-2 every 3 weeks, has been assessed in three phase II trials of ovarian, renal and colorectal cancer. In general terms the drug...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1995.498
更新日期:1995-11-01 00:00:00
abstract::In a previous study we found that aromatic amines, particularly 4-aminobiphenyl, formed haemoglobin adducts at higher concentrations in the blood of smokers compared to non-smokers. We re-analyse here data on haemoglobin adducts of 14 aromatic amines in order to ascertain if the inter-individual variability left unexp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.120
更新日期:1990-04-01 00:00:00
abstract::Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990-2003. We compared incidence rates among new ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605024
更新日期:2009-05-05 00:00:00
abstract::Diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is currently based on phenotypical analysis of an expanded pedigree. Diagnostic guidelines ('Amsterdam criteria') proposed by the International Collaborative Group on HNPCC are often too stringent for use with small families. There is also the possibility...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.508
更新日期:1995-11-01 00:00:00
abstract::A possible link between protein kinase C (PKC) and P-glycoprotein (P-gp)-mediated-multidrug resistance (MDR) was assumed from studies on MDR cell lines selected in vitro. The functional relevance of PKC for the MDR phenotype remains unclear, and the involvement of a particular PKC isozyme in clinically occurring drug ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.13
更新日期:1998-01-01 00:00:00
abstract::We investigated the effects of interleukin-2 (IL-2) exposure on T-cell signal transduction molecules and apoptosis markers in tumour-infiltrating lymphocytes (TIL) isolated from 20 melanoma and 16 colorectal carcinoma metastases and expanded in vitro for therapeutic reinfusion. Before IL-2 culture, TIL showed undetect...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600679
更新日期:2003-01-27 00:00:00
abstract:BACKGROUND:Here, we explore the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases, including members of the Src kinase family, EphA2, and focal adhesion kinase for the treatment of ovarian cancer. METHODS:We examined the effects of dasati...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605381
更新日期:2009-11-17 00:00:00
abstract::Cancer Research UK has recently sponsored a meeting, organized by the UK Medical Research Council, on cancer drug resistance. Several of the molecular mechanisms responsible for this clinical outcome, such as DNA interstrand crosslink repair, apoptosis evasion, cytochrome P450 and P-glycoprotein, were discussed. There...
journal_title:British journal of cancer
pub_type:
doi:10.1038/sj.bjc.6602821
更新日期:2005-10-31 00:00:00
abstract::In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplat...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/bjc.1998.393
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.188
更新日期:2013-05-28 00:00:00
abstract::In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (T(reg)), Th17, natural killer (NK) and NK T (NKT) cells before, dur...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604963
更新日期:2009-04-07 00:00:00
abstract::This study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chem...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1054/bjoc.2001.1902
更新日期:2001-07-20 00:00:00
abstract::Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after tr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604180
更新日期:2008-01-29 00:00:00
abstract:BACKGROUND:To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacokinetics (PK) and pharmacodynamics...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.332
更新日期:2011-09-27 00:00:00
abstract::The purpose of this study was to determine the maximum-tolerated dose of gemcitabine plus mitoxantrone in women with metastatic breast cancer (MBC) and to evaluate activity and toxicity of this combination in a phase II trial. Sixty-three patients with MBC, previously treated with chemotherapy including anthracycline ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6600780
更新日期:2003-02-24 00:00:00
abstract::Caffeine has for many years been known to be involved in the sensitization of DNA to damage. One potential mechanism recently put forward is an override of the G2/M block induced by irradiation, which would leave the cells less time for DNA repair prior to mitosis. However, different cell types display a variety of re...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1259
更新日期:2000-08-01 00:00:00
abstract::Transformation of primary hamster embryo cells was investigated using 3-methylcholanthrene (MCA), a combination of MCA and 12-O-tetradecanoylphorbol-13-acetate (TPA), and initiation with MCA or dibenz(a,h)anthracene (DBA) followed by promotion with TPA. Evidence for transformation was (a) abnormal cellular morphology,...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1979.2
更新日期:1979-01-01 00:00:00
abstract::Chinese hamster V79-171B spheroids implanted in the peritoneal cavity of C3H mice were characterized as a model for evaluating the toxicity of drugs requiring metabolic activation in vivo. After 24 hours in the peritoneal cavity, spheroid cellularity and plating efficiency were not significantly decreased, and host ce...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.196
更新日期:1987-09-01 00:00:00
abstract::To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five -amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1-16 mg kg(-1)), receiving ATN-161 administered as a 10-min infusion th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603171
更新日期:2006-06-05 00:00:00
abstract::The carcinoembryonic antigen (CEA) was produced and released by human colorectal carcinomata and also the normal attached mucosa when maintained in both monolayer and organ culture. Immunoperoxidase cytochemical methods were employed for the cellular localization of CEA which was demonstrable only on the neoplastic ce...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.97
更新日期:1975-05-01 00:00:00
abstract::The prognostic weight of histological and biological factors was compared with that of known clinical prognostic factors in a population of 108 consecutive previously untreated patients with head and neck squamous cell carcinoma. Parameters studied were: tumour vascularisation, mitotic index, histological differentiat...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.92
更新日期:1996-02-01 00:00:00
abstract::In locally advanced undifferentiated nasopharyngeal carcinoma (UNPC), concomitant chemo-radiotherapy is the only strategy that gave better results over radiation alone in a phase III trial. Adding effective chemotherapy to a concomitant chemo-radiotherapy programme may be a way to improve the results further. 30 patie...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1054/bjoc.2000.1485
更新日期:2000-12-01 00:00:00
abstract::Several radiotherapeutic schedules compatible with continued structural-functional integrity of the gastrointestinal (GI) mucosa were compared utilizing the P815X2 murine mastocytoma grown as a solid subcutaneous tumour. Both the tumour and underlying normal tissues were irradiated during the treatments. The tumour ex...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.29
更新日期:1975-02-01 00:00:00
abstract::Four-coordinate (Pt(II)) platinum-based anticancer drugs are widely used in primary or palliative chemotherapy and produce considerable efficacy in certain clinical applications, for example testicular cancer. However, in many cancers the Pt(II) drugs are beset by poor efficacy mainly due to suboptimal pharmacokinetic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603854
更新日期:2007-07-16 00:00:00
abstract::Imaging has an essential role in the planning and delivery of radiotherapy. Recent advances in imaging have led to the development of advanced radiotherapy techniques-including image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy and proton beam therapy. The optimal use of imagin...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/s41416-019-0412-y
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Non-invasive biomarkers of disease progression in mice with cancer are lacking making it challenging to implement appropriate humane end points. We investigated whether body temperature, food and water consumption could be used to predict tumour burden. METHODS:Thirty-six male, wild-type C57Bl/6 mice were i...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.818
更新日期:2014-02-18 00:00:00
abstract::Photodynamic therapy (PDT) using Photofrin was used in combination with a hypoxic toxin (mitomycin C, MMC) to treat four patients with recurrent skin metastasis of a mammary carcinoma. In preclinical experiments an additive effect was found for the combination of MMC and PDT for treating subcutaneous RIF1 tumours in m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.186
更新日期:1996-04-01 00:00:00
abstract::Emerging evidences suggest the existence of a new mode of epidermal growth factor receptor (EGFR) signalling pathway in which activated EGFR undergoes nuclear translocalization and subsequently regulates gene expression and potentially mediates other cellular processes. This signalling route is distinct from the bette...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Novel treatment strategies in Ewing sarcoma include targeted cellular therapies. Preclinical in vivo models are needed that reflect their activity against systemic (micro)metastatic disease. METHODS:Whole-body magnetic resonance imaging (WB-MRI) was used to monitor the engraftment and dissemination of human...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.356
更新日期:2013-08-06 00:00:00
abstract::The phenotypic expression of cells derived from human anaplastic astrocytomas, rat glioma, normal human adult and foetal brain tissue have been examined for differentiated and malignancy-associated properties. Glial fibrillary acidic protein (GFAP), high affinity glutamate and gamma-amino butyric acid (GABA) uptake an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.44
更新日期:1984-03-01 00:00:00