Early Detection related publications from the University of Cambridge

Robust, universal biomarker assay to detect senescent cells in biological specimens

Evangelou K, Lougiakis N, Rizou SV, Kotsinas A, Kletsas D, Muñoz-Espín D, Kastrinakis NG, Pouli N, Marakos P, Townsend P, Serrano M, Bartek J and Gorgoulis VG.

Aging Cell. November 17, 2016, doi: 10.1111/acel.12545

Cellular senescence contributes to organismal development, aging, and diverse pathologies, yet available assays to detect senescent cells remain unsatisfactory. This publication proposes a new hybrid histo-/immunochemical method, easy to perform, reliable, and universally applicable to assess senescence in biomedicine, from cancer research to gerontology.

Development of a comprehensive genotype-to-fitness map of adaption-driving mutations in yeast

Venkataram S, Dunn B, Li Y, Agarwala A, Chang J, Ebel ER, Geiler-Samerotte K, Hérissant L, Blundell JR, Levy SF and Fisher DS.

CellPress volume 166, Issue 6. September 8 2016, doi: 10.1016/j.cell.2016.08.002

Adaptive evolution plays a large role in generating the phenotypic diversity observed in nature, yet current methods are impractical for characterizing the molecular basis and fitness effects of large numbers of individual adaptive mutations. In this publication, a DNA barcoding approach was used to generate the genotype-to-fitness map for adaptation-driving mutations from a Saccharomyces cerevisiae population experimentally evolved by serial transfer under limiting glucose.

Design and validation of a near-infrared fluorescence endoscope for detection of early esophageal malignancy

Waterhouse DJ, Joseph J, Neves AA, di Pietro M, Brindle KM, Fitzgerald RC, Bohndiek SE.

J. Biomed. Opt. 21(8), 084001 (Aug 04, 2016). doi:10.1117/1.JBO.21.8.084001.

This paper describes the synthesis of near-infrared (NIR) fluorescent wheat germ agglutinin (WGA-IR800CW) and the construction of a clinically translatable bimodal NIR and white light endoscope to combat the lack of contrast in white light endoscopy when imaging patients with suspected Barrett’s oesophagus.

Regulators of genetic risk of breast cancer identified by integrative network analysis

Castro MAA, de Santiago I, Campbell TM, Vaughn C, Hickey TE, Ross E, Tilley WD, Markowetz F, Ponder BA, Meyer KB.

Nat Genet. 48(1):12-21 (2016).

The network approach used here provides a foundation for determining the regulatory circuits governing breast cancer as well as other disease settings, to identify targets for intervention.

Analysis of dysplasia in patients with Barrett’s esophagus based on expression pattern of 90 genes

Varghese S, Newton R, Ross-Innes CS, Lao-Sirieix P, Krishnadath KK, O’Donovan M, Novelli M, Wernisch L, Bergman J, Fitzgerald RC.

Gastroenterology 2015 Nov 149(6) 1511-18 Epub 2015.

This paper discovers and validates a 90 gene panel to accurately identify patients with low grade dysplasia in Barrett’s oesophagus who are at high risk of progression.

Single-pixel phase-corrected fiber bundle endomicroscopy with lensless focussing capability.

Gordon GSD, Joseph J, Bohndiek SE, Wilkinson TD.

J. Lightwave Technol, 2015, 33 (16): 3419-3425.

This study paves the way for the use of optical phase for lensless focusing in endoscopy.

Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin

Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P, McLaren S, Wedge DC, Fullam A, Alexandrov LB, Tubio JM, Stebbings L, Menzies A, Widaa S, Stratton MR, Jones PH*, Campbell PJ*. (*co-corresponding authors).

Science 2015, 880-86. May 22, 2015. 348, doi: 10.1126/science.aaa6806

This paper describes how aged sun-exposed skin is a patchwork of thousands of evolving clones with over a quarter of cells carrying cancer-causing mutations while maintaining the physiological functions of the epidermis.

Symptoms and other factors associated with time to presentation and diagnosis and stage at diagnosis of lung cancer: a prospective cohort study

Walter FM, Rubin G, Bankhead C, Morris HC, Hall N, Mills K, Dobson C, Rintoul R, Hamilton W and Emery J.

Brit J Cancer. 2015 Mar 31;112 Suppl: S6-S13. doi: 10.1038/bjc.2015.30. PMID: 25734397.

This study found that haemoptysis is the strongest symptom predictor of lung cancer but occurs in only a fifth of patients, calling for programmes of early diagnosis to focus on multiple symptoms and their evolution.

Dissecting the role of the ϕ29 terminal protein DNA binding residues in viral DNA replication

Holguera I, Muñoz-Espín D and Salas M.

Nucleic Acids Research. February 26, 2015, doi: 10.1093/nar/gkv127

This publication describes the involvement of the TP N-terminal domain residues responsible for DNA binding in the different stages of viral DNA replication by assaying the in vitro activity of purified TP N-terminal mutant proteins.

Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett’s esophagus: a multi-centre case-control study

Ross-Innes CS, Debiram-Beecham I, O'Donovan M, Walker E, Varghese S, Lao-Sirieix P, Lovat L, Griffin M, Ragunath K, Haidry R, Sami SS, Kaye P, Novelli M, Disep B, Ostler R, Aigret B, North BV, Bhandari P, Haycock A, Morris D, Attwood S, Dhar A, Rees C, Rutter MD, Sasieni PD, Fitzgerald RC.

BEST2 Study Group. PLoS Med 2015 Jan 29;12(1) eCollection 2015 Jan.

This paper describes the results of a case:control study using the Cytosponge in over 1,000 patients and shows that it is safe, acceptable and has a high degree of accuracy.

Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis

Weaver JMJ, Ross-Innes C, Shannon N, Lynch AG, Forshew T, Barbera M, Murtaza M, Ong C-AJ, Lao-Sirieix P, Dunning MJ, Smith L, Smith ML, Anderson CL, Carvalho B, O'Donovan M, Underwood TJ, May AP, Grehan N, Hardwick R, Davies J, Oloumi A, Aparicio S, Caldas C, Eldridge MD, Edwards PA, Rosenfeld N, Tavaré S and Fitzgerald RC.

OCCAMS Consortium. (2014) Nat Genet. 2014 Aug;46(8):837-43. doi: 10.1038/ng.3013. Epub 2014 Jun 22.

This paper demonstrates for the first time that somatic mutations occur early in pre-invasive disease and careful ordering of events is required in order to develop effective biomarker strategies for Early Detection.

Breast-cancer risk in families with mutations in PALB2

Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J, Lee A, Subramanian D, De Leeneer K, Fostira F, Tomiak E, Neuhausen SL, Teo ZL, Khan S, Aittomäki K, Moilanen JS, Turnbull C, Seal S, Mannermaa A, Kallioniemi A, Lindeman GJ, Buys SS, Andrulis IL, Radice P, Tondini C, Manoukian S, Toland AE, Miron P, Weitzel JN, Domchek SM, Poppe B, Claes KB, Yannoukakos D, Concannon P, Bernstein JL, James PA, Easton DF, Goldgar DE, Hopper JL, Rahman N, Peterlongo P, Nevanlinna H, King MC, Couch FJ, Southey MC, Winqvist R, Foulkes WD and Tischkowitz M.

N Engl J Med. 2014, Aug 7 2014;371(6):497-506.

This study determined that loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer, with respect to both frequency of mutations and risk associated with them.

Preferences for cancer investigation: a vignette-based study of primary care attenders

Banks J, Hollinghurst S, Bigwood L, Peters TJ, Walter FM and Hamilton W.

Lancet Oncol. 2014;15(2):232-40. doi: 10.1016/S1470-2045(13)70588-6.

This paper investigated the barriers to presentation in primary care, symptom recognition and referral for specialist investigation in lung, pancreatic and colorectal cancers.

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.

Pharoah PD, Tsai YY, Ramus SJ, Phelan CM, Goode EL, Lawrenson K, et al.

Nat Genet. 45, 362-70 (2013).

The result of this study was evidence for functional mechanisms underlying susceptibility and pathogenesis of ovarian cancer.

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