P Quirke

Roche Institute of Molecular Biology, Nutley, New Jersey, United States

Are you P Quirke?

Claim your profile

Publications (290)1971.69 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic colorectal cancer (mCRC). Experimental Design: A pooled analysis of four phase III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN and FOCUS) was performed. Primary outcome parameter was the hazard ratio (HR) for median progression-free survival (PFS) and overall survival (OS) in relation to MMR and BRAF. For the pooled analysis, Cox regression analysis was performed on individual patient data. Results: The primary tumors of 3063 patients were analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a BRAF(MT). BRAF(MT) was observed in 53 (34.6%) of patients with dMMR tumors compared to 197 (6.8%) of patients with proficient MMR (pMMR) tumors (p<0.001). In the pooled data set, median PFS and OS were significantly worse for patients with dMMR compared to pMMR tumors (HR 1.33, 95% CI 1.12-1.57 and HR 1.35, 95% CI 1.13-1.61, respectively), and for patients with BRAF(MT) compared to BRAF wild-type (BRAF(WT)) tumors (HR 1.34, 95% CI 1.17-1.54 and HR 1.91, 95% CI 1.66-2.19, respectively). PFS and OS were significantly decreased for patients with BRAF(MT) within the group of patients with pMMR, but not for BRAF status within dMMR, or MMR status within BRAF(WT) or BRAF(MT). Conclusions: Prevalence of dMMR and BRAF(MT) in mCRC patients is low and both biomarkers confer an inferior prognosis. Our data suggest that the poor prognosis of dMMR is driven by BRAF(MT) status.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Complete mesocolic excision with central vascular ligation (CME) produces an optimal colonic cancer specimen. The ability of expert laparoscopic surgeons to produce equivalent specimens is unknown.Methods Fresh specimen photographs and clinicopathological data from patients undergoing laparoscopically assisted CME at St Mark's Hospital, Harrow, were submitted for independent pathological review. Surgery was performed by a mixture of consultant specialists and trainees under consultant specialist supervision, between February 2010 and July 2011. The planes of surgery were graded and tissue morphometry was performed using standard methods. The results were compared with published data from open CME and non-CME surgery.ResultsIn total, 69 patients were identified, and in 96 per cent resection was performed completely or partially by surgical trainees. Laparoscopic CME produced a similar specimen to open CME. The laparoscopic mesocolic plane resection rate was similar to that for open surgery (90 versus 88 per cent). The distance between the bowel wall and site of vascular division was similar for laparoscopic and open right-sided CME (92 versus 95 mm respectively). The corresponding values for left-sided CME were also similar (103 versus 107 mm). Compared with values from two non-CME series, laparoscopic CME had a higher mesocolic plane rate (90 versus 40 and 48 per cent), and resected more tissue between the bowel wall and the vascular division (right-sided: 92 versus 72 and 76 mm; left-sided: 103 versus 85 and 70 mm). The lymph node yield remained low following laparoscopic CME compared with open CME (median 18 versus 32; P < 0·001) and identical to that of non-CME surgery (median 18).Conclusion Laparoscopic CME can be performed to the same standard as open surgery by supervised trainees. However, this did not increase the lymph node yield.
    British Journal of Surgery 08/2014; · 4.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Most cancers arise and evolve as a consequence of somatic mutations. These mutations influence tumor behavior and clinical outcome. Consequently, there is considerable interest in identifying somatic variants within specific genes (such as BRAF, KRAS and EGFR) so that chemotherapy can be tailored to the patient's tumor genotype rather than using a generic treatment based on histological diagnosis alone. Owing to the heterogeneous nature of tumors, a somatic mutation may be present in only a subset of cells, necessitating the use of quantitative techniques to detect rare variants. The highly quantitative nature of next-generation sequencing (NGS), together with the ability to multiplex numerous samples, makes NGS an attractive choice with which to screen for somatic variants. However, the large volumes of sequence data present significant difficulties when applying NGS for the detection of somatic mutations. To alleviate this, we have developed methodologies including a set of data analysis programs, which allow the rapid screening of multiple formalin-fixed, paraffin-embedded samples for the presence of specified somatic variants using unaligned Illumina NGS data.Laboratory Investigation advance online publication, 28 July 2014; doi:10.1038/labinvest.2014.96.
    07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal adenomas measuring ten millimetres or more are at increased neoplastic risk and therefore undergo more rigorous follow up. Currently there is no standardised method of assessing polyp size. We aimed to determine the correlation between endoscopic and histopathological measurements to determine the most appropriate method for clinical use.
    Histopathology 06/2014; · 2.86 Impact Factor
  • Article: Response.
    CancerSpectrum Knowledge Environment 04/2014; · 14.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies.Patients and Methods:Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload.Results:A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival.Conclusions:Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.British Journal of Cancer advance online publication, 17 April 2014; doi:10.1038/bjc.2014.182 www.bjcancer.com.
    British Journal of Cancer 04/2014; · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A key factor in the prognosis of colorectal cancer, and its response to chemoradiotherapy, is the ratio of cancer cells to surrounding tissue (the so called tumour:stroma ratio). Currently tumour:stroma ratio is calculated manually, by examining H&E; stained slides and counting the proportion of area of each. Virtual slides facilitate this analysis by allowing pathologists to annotate areas of tumour on a given digital slide image, and in-house developed stereometry tools mark random, systematic points on the slide, known as spots. These spots are examined and classified by the pathologist. Typical analyses require a pathologist to score at least 300 spots per tumour. This is a time consuming (10- 60 minutes per case) and laborious task for the pathologist and automating this process is highly desirable. Using an existing dataset of expert-classified spots from one colorectal cancer clinical trial, an automated tumour:stroma detection algorithm has been trained and validated. Each spot is extracted as an image patch, and then processed for feature extraction, identifying colour, texture, stain intensity and object characteristics. These features are used as training data for a random forest classification algorithm, and validated against unseen image patches. This process was repeated for multiple patch sizes. Over 82,000 such patches have been used, and results show an accuracy of 79%, depending on image patch size. A second study examining contextual requirements for pathologist scoring was conducted and indicates that further analysis of structures within each image patch is required in order to improve algorithm accuracy.
    02/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A number of studies have demonstrated that lymph node metastasis is a poor prognostic factor in colon cancer. Advances of surgical procedure have improved the outcomes of colon cancer treatment. The aim of this study was to compare the characteristics of surgery for stage III colon cancer between England, Germany, and Japan. Using the data of patients with colon cancer from one English, one German, and two Japanese centers, the characteristics of clinicopathologic features were compared. Conventional surgery, complete mesocolic excision (CME) with central vascular ligation, and D3 lymph node dissection were performed in England, Germany, and Japan, respectively. Nineteen English, 26 German, and 60 Japanese patients were enrolled. There was no difference in tumor location, pT, and pN factors among the three groups. The length of resected bowel and the area of resected mesentery of the English and CME specimens were significantly greater than those of the D3 specimens (P < 0.0001 and P < 0.0001, respectively), whereas the length of the vascular tie to the bowel wall was similar between the CME and D3 specimens (P = 0.87), which was longer than that of the English specimens. The number of lymph nodes retrieved in the CME specimens was greatest among three groups (P < 0.0001), although the number of positive nodes was comparable (P = 0.64). The rates of mesocolic plane surgery in the English, CME, and D3 specimens were 47.4, 88.5, and 71.7 %, respectively (P = 0.022). Three types of surgery for colon cancer differed in terms of the length of the resected bowel and the area of mesentery, although the length of the vascular tie to the bowel wall was similar between CME and D3 specimens. The high rates of mesocolic plane surgery were demonstrated in the CME and D3 specimens.
    Annals of Surgical Oncology 02/2014; · 4.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been evident for a while that the result after resection for colon cancer may not have been optimal. Several years ago, this was showed by some leading surgeons in the USA but a concept of improving results was not consistently pursued. Later, surgeons in Europe and Japan have increasingly adopted the more radical principle of complete mesocolic excision (CME) as the optimal approach for colon cancer. The concept of CME is a similar philosophy to that of total mesorectal excision for rectal cancer and precise terminology and optimal surgery are key factors. There are three essential components to CME. The main component involves a dissection between the mesenteric plane and the parietal fascia and removal of the mesentery within a complete envelope of mesenteric fascia and visceral peritoneum that contains all lymph nodes draining the tumour area (Hohenberger et al., Colorectal Disease 11:354-365, 2009; West et al., J Clin Oncol 28:272-278, 2009). The second component is a central vascular tie to completely remove all lymph nodes in the central (vertical) direction. The third component is resection of an adequate length of bowel to remove involved pericolic lymph nodes in the longitudinal direction. The oncological rationale for CME and various technical aspects of the surgical management will be explored. The consensus conference agreed that there are sound oncological hypotheses for a more radical approach than has been common up to now. However, this may not necessarily apply in early stages of the tumour stage. Laparoscopic resection appears to be equally well suited for resection as open surgery.
    International Journal of Colorectal Disease 01/2014; · 2.24 Impact Factor
  • P Quirke, N P West, I D Nagtegaal
    [Show abstract] [Hide abstract]
    ABSTRACT: Care for patients with colon and rectal cancer has improved in the last 20 years; however, a considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organizations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 01/2014; · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim Over recent years there has been a new focus on the quality of colon cancer surgery following the description and introduction of complete mesocolic excision (CME). In the same period, laparoscopic surgery has been widely applied to the treatment of colon cancer. We aimed to evaluate the introduction of both CME and laparoscopic-assisted surgery at Aarhus University Hospital, Denmark between 2008 and 2011. Secondly we aimed to evaluate the impact on the quality of surgery of post-operative team meetings where pathologists demonstrated the plane of surgery on the specimens. Method A series of 209 consecutive and prospectively collected colon cancer specimens were evaluated by assessing the plane of surgery and measuring the amount of tissue resected. Multivariate analyses were used to control for influencing factors. Results The proportion of specimens resected in the mesocolic plane was high and increased significantly following the introduction of post-operative team meetings (52 % to 76 %, p = 0.02). Laparoscopic surgery enhanced the distance between the tumour and the arterial tie by a mean of 27 mm (p < 0.0001) and the distance between the nearest bowel wall and the arterial tie by 26 mm (p < 0.0001) when compared to an open approach. Factors such as body mass index and age influenced the outcome for surgical quality. Conclusion Implementation of CME and laparoscopic-assisted surgery for colon cancer is a challenge and requires continuous training and feedback. Post-operative multidisciplinary team meetings may be a key element in this process.
    European Journal of Surgical Oncology (EJSO). 01/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR). Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates. Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis. High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.
    Journal of Clinical Oncology 11/2013; · 18.04 Impact Factor
  • Colorectal Disease 11/2013; 15(11):1358-60. · 2.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and metastatic colorectal disease separately. Moreover, evidence based algorithms for diagnostics and treatment were composed which were also submitted to the Delphi process. The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. Multidisciplinary consensus on key diagnostic and treatment issues for colon and rectal cancer management using the Delphi method was successful. This consensus document embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.
    European journal of cancer (Oxford, England: 1990) 10/2013; · 4.12 Impact Factor
  • Source
    EJC Supplements 09/2013; 11(2):60–71. · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report herein the development of a simple, sensitive colorimetric magnetic nanoparticle (MNP)- enzyme based DNA sandwich assay that is suitable for simultaneous, label-free quantitation of two DNA targets down to 50 fM level. It can also effectively discriminate single-nucleotide polymorphisms (SNPs) in genes associated with human cancers (KRAS codon 12/13 SNPs). This assay uses a pair of specific DNA probes, one being covalently conjugated to a MNP for target capture while the other being linked to an enzyme for signal amplification, to sandwich a DNA target, allowing for convenient magnetic separation and subsequently efficient enzymatic signal amplification for high sensitivity. Careful optimization of the MNP surfaces and assay conditions greatly reduced the background, allowing for sensitive, specific detection of as little as 5 attomole (50 fM in 100 υL) of target-DNA. Moreover, this sensor is robust, it can effectively discriminate cancer specific SNPs against the wild-type non-cancer target, and works efficiently in 10% human serum. Furthermore, this sensor can simultaneously quantitate two different DNA targets by using two pairs of unique capture- and signal- DNA probes specific for each target. This general, simple and sensitive DNA sensor appears to be well-suited for a wide range of genetics based biosensing and diagnostic applications.
    Analytical Chemistry 08/2013; 85:9238−9244. · 5.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biallelic inherited mutations in the oxidative DNA damage repair gene MUTYH predispose to colorectal adenomas and colorectal carcinoma (CRC) with high penetrance. We investigated whether rare inherited variants in other oxidative DNA damage repair genes predisposed to CRC. Single marker association analyses were assessed under an allelic model with Bonferroni correction for multiple testing. All statistical tests were two-sided. A rare inherited nonsynonymous variant in OGG1 (Gly308Glu), the functional partner of MUTYH, was over-represented in case patients with advanced CRC compared with population-based control subjects (n = 36 of 2142 case patients vs n = 15 of 2175 control subjects in the training phase, P = 1.8×10(-3); and n = 22 of 1005 case patients vs n = 8 of 1389 control subjects in the validation phase, P = 4.8×10(-4); P = 1.4×10(-5) combined; odds ratio = 2.92, 95% confidence interval = 1.80 to 4.74). Glycine at residue 308 was highly conserved through evolution, and the glutamic acid substitution was predicted as likely to interfere with function. Biallelic inherited and somatic OGG1 mutations were rarely observed in OGG1 (Gly308Glu) carriers, nor did we find any associated somatic mutator phenotype. These data suggest that OGG1 (Gly308Glu) may act as a low-penetrance allele that contributes to colorectal tumorigenesis.
    CancerSpectrum Knowledge Environment 07/2013; · 14.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. METHODS: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. RESULTS: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. CONCLUSIONS: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.
    European journal of cancer (Oxford, England: 1990) 06/2013; · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Current methods for resolving genetically distinct subclones in tumour samples require somatic mutations to be clustered by allelic frequencies, which are determined by applying a variant calling program to next-generation sequencing data. Such programs were developed to accurately distinguish true polymorphisms and somatic mutations from the artifactual non-reference alleles introduced during library preparation and sequencing. However, numerous variant callers exist with no clear indication of the best-performer for subclonal analysis, in which the accuracy of the assigned variant frequency is as important as correctly indicating whether the variant is present or not. Furthermore, sequencing depth (the number of times that a genomic position is sequenced) affects the ability to detect low-allelic fraction variants and accurately assign their allele frequencies. We created two synthetic sequencing datasets, and sequenced real KRAS amplicons, with variants spiked in at specific ratios, in order to assess which caller performs best in terms of both variant detection and assignment of allelic frequencies. We also assessed the sequencing depths required to detect low-allelic fraction variants. We found that VarScan2 performed best overall with sequencing depths of 100x, 250x, 500x and 1000x required to accurately identify variants present at 10%, 5%, 2.5% and 1% respectively. This article is protected by copyright. All rights reserved.
    Human Mutation 06/2013; · 5.21 Impact Factor
  • Source
    Yue Zhang, Yuan Guo, Philip Quirke, Dejian Zhou
    [Show abstract] [Hide abstract]
    ABSTRACT: We report herein the development of a highly sensitive and selective approach for label-free DNA detection by combining target-recycled ligation (TRL), magnetic nanoparticle assisted target capture/separation, and efficient enzymatic amplification. We show that our approach can detect as little as 30 amol (600 fM in 50 μL) of unlabelled single-stranded DNA targets and offer an exquisitely high discrimination ratio (up to >380 fold with background correction) between a perfect-match cancer mutant and its single-base mismatch (wild-type) DNA target. Furthermore, it can quantitate the rare cancer mutant (KRAS codon 12) in a large excess of coexisting wild-type DNAs down to 0.75%. This sensor appears to be well-suited for sensitive SNP detection and a wide range of DNA mutation based diagnostic applications.
    Nanoscale 05/2013; 5(11):5027-5035. · 6.73 Impact Factor

Publication Stats

12k Citations
1,971.69 Total Impact Points

Institutions

  • 2014
    • Roche Institute of Molecular Biology
      Nutley, New Jersey, United States
  • 1984–2014
    • University of Leeds
      • • School of Medicine
      • • Leeds Institute of Molecular Medicine (LIMM)
      • • Division of Clinical Trials Research
      • • Division of Reproduction and Early Development
      Leeds, England, United Kingdom
  • 2011–2013
    • The Institute for Molecular Medicine
      Huntington Beach, California, United States
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2006–2013
    • Saint James School Of Medicine
      Park Ridge, Illinois, United States
    • University of West London
      Londinium, England, United Kingdom
  • 2007–2012
    • St. James University
      Saint James, New York, United States
  • 1992–2012
    • Leeds Teaching Hospitals NHS Trust
      Leeds, England, United Kingdom
    • Queen's University Belfast
      Béal Feirste, N Ireland, United Kingdom
    • The Kings College
      Brooklyn, New York, United States
  • 2010–2011
    • Institute of Genetics and Molecular Medicine
      Edinburgh, Scotland, United Kingdom
  • 2006–2011
    • Radboud University Nijmegen
      • Department of Pathology
      Nijmegen, Provincie Gelderland, Netherlands
  • 2005
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
  • 1998
    • Semmelweis University
      • First Department of Obstetrics and Gynaecology
      Budapest, Budapest fovaros, Hungary
  • 1996
    • Centre for Digestive Diseases
      Newtown, New South Wales, Australia
    • Sapienza University of Rome
      • Department of Experimental Medicine
      Roma, Latium, Italy
  • 1991–1992
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      • Department of Anatomical pathology
      Giovanni Rotondo, Apulia, Italy
  • 1990
    • ICL
      Londinium, England, United Kingdom
  • 1989
    • The University of Edinburgh
      • Division of Pathology
      Edinburgh, Scotland, United Kingdom
  • 1987
    • University of Sydney
      Sydney, New South Wales, Australia