Welcome to The Christie Research Publications Repository

The repository contains the research outputs from staff and students at The Christie NHS Foundation Trust and Cancer Research UK Manchester Institute.

Current Repository Content:

Over 7000 peer reviewed articles, reviews and selected publications from 1933 onwards.

Find out more....

We upload data monthly to the repository. To find out more about the repository, article submission or for advice on how to search it:

Please contact Kostoris Library on 0161 446 3456/3455.


  • In silico error correction improves cfDNA mutation calling.

    Kim Chang, S; Mohan, Sumitra; Ayub, Mahmood; Rothwell, Dominic G; Dive, Caroline; Brady, Ged; Miller, Crispin J; Clinical and Experimental Pharmacology Group, University of Manchester, Alderley Park, Manchester, UK (2018)
    Motivation: Circulating-free DNA (cfDNA) profiling by sequencing is an important minimally invasive protocol for monitoring the mutation profile of solid tumours in cancer patients. Since the concentration of available cfDNA is limited, sample library generation relies on multiple rounds of PCR amplification, during which the accumulation of errors results in reduced sensitivity and lower accuracy.Results: We present PCR Error Correction (PEC), an algorithm to identify and correct errors in short read sequencing data. It exploits the redundancy that arises from multiple rounds of PCR amplification. PEC is particularly well suited to applications such as single-cell sequencing and circulating tumour DNA (ctDNA) analysis, in which many cycles of PCR are used to generate sufficient DNA for sequencing from small amounts of starting material. When applied to ctDNA analysis, PEC significantly improves mutation calling accuracy, achieving similar levels of performance to more complex strategies that require additional protocol steps and access to calibration DNA datasets. Availability and implementation: PEC is available under the GPL-v3 Open Source licence, and is freely available from: https://github.com/CRUKMI-ComputationalBiology/PCR_Error_Correction.git. Supplementary information: Supplementary figures are available at Bioinformatics online.
  • miRNA-mediated TUSC3 deficiency enhances UPR and ERAD to promote metastatic potential of NSCLC.

    Jeon, YJ; Kim, T; Park, D; Nuovo, GJ; Rhee, S; Joshi, P; Lee, BK; Jeong, J; Suh, SS; Grotzke, JE; Kim, SH; Song, J; Sim, H; Kim, Y; Peng, Y; Jeong, Y; Garofalo, Michela; Zanesi, N; Kim, J; Liang, G; Nakano, I; Cresswell, P; Nana-Sinkam, P; Cui, R; Croce, CM; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA (2018)
    Non-small cell lung carcinoma (NSCLC) is leading cause of cancer-related deaths in the world. The Tumor Suppressor Candidate 3 (TUSC3) at chromosome 8p22 known to be frequently deleted in cancer is often found to be deleted in advanced stage of solid tumors. However, the role of TUSC3 still remains controversial in lung cancer and context-dependent in several cancers. Here we propose that miR-224/-520c-dependent TUSC3 deficiency enhances the metastatic potential of NSCLC through the alteration of three unfolded protein response pathways and HRD1-dependent ERAD. ATF6?-dependent UPR is enhanced whereas the affinity of HRD1 to its substrates, PERK, IRE1? and p53 is weakened. Consequently, the alteration of UPRs and the suppressed p53-NM23H1/2 pathway by TUSC3 deficiency is ultimately responsible for enhancing metastatic potential of lung cancer. These findings provide mechanistic insight of unrecognized roles of TUSC3 in cancer progression and the oncogenic role of HRD1-dependent ERAD in cancer metastasis.
  • Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma.

    Trucco, Lucas D; Mundra, Piyushkumar A; Hogan, Kate; Garcia-Martinez, Pablo; Viros, Amaya; Mandal, Amit Kumar; Macagno, N; Gaudy-Marqueste, C; Allan, D; Baenke, Franziska; Cook, Martin G; McManus, Clare; Sanchez-Laorden, Berta; Dhomen, Nathalie; Marais, Richard; Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK (2018)
    Erratum in Publisher Correction: Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma. [Nat Med. 2018] Abstract The melanoma genome is dominated by ultraviolet radiation (UVR)-induced mutations. Their relevance in disease progression is unknown. Here we classify melanomas by mutation signatures and identify ten recurrently mutated UVR signature genes that predict patient survival. We validate these findings in primary human melanomas; in mice we show that this signature is imprinted by short-wavelength UVR and that four exposures to UVR are sufficient to accelerate melanomagenesis.
  • Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma.

    Menotti, Matteo; Ambrogio, C; Cheong, TC; Pighi, C; Mota, I; Cassel, SH; Compagno, M; Wang, Q; Dall'Olio, R; Minero, VG; Poggio, T; Sharma, GG; Patrucco, E; Mastini, C; Choudhari, R; Pich, A; Zamo, A; Piva, R; Giliani, S; Mologni, L; Collings, CK; Kadoch, C; Gambacorti-Passerini, C; Notarangelo, LD; Anton, IM; Voena, C; Chiarle, R; Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy (2018)
    In T lymphocytes, the Wiskott-Aldrich Syndrome protein (WASP) and WASP-interacting-protein (WIP) regulate T cell antigen receptor (TCR) signaling, but their role in lymphoma is largely unknown. Here we show that the expression of WASP and WIP is frequently low or absent in anaplastic large cell lymphoma (ALCL) compared to other T cell lymphomas. In anaplastic lymphoma kinase-positive (ALK+) ALCL, WASP and WIP expression is regulated by ALK oncogenic activity via its downstream mediators STAT3 and C/EBP-?. ALK+ lymphomas were accelerated in WASP- and WIP-deficient mice. In the absence of WASP, active GTP-bound CDC42 was increased and the genetic deletion of one CDC42 allele was sufficient to impair lymphoma growth. WASP-deficient lymphoma showed increased mitogen-activated protein kinase (MAPK) pathway activation that could be exploited as a therapeutic vulnerability. Our findings demonstrate that WASP and WIP are tumor suppressors in T cell lymphoma and suggest that MAP-kinase kinase (MEK) inhibitors combined with ALK inhibitors could achieve a more potent therapeutic effect in ALK+ ALCL.
  • Molecular evolution of early-onset prostate cancer identifies molecular risk markers and clinical trajectories.

    Gerhauser C; Favero F; Risch T; Simon R; Feuerbach L; Assenov Y; Heckmann D; Sidiropoulos N; Waszak SM; Hubschmann D; Urbanucci A; Girma EG; Kuryshev V; Klimczak LJ; Saini N; Stutz AM; Weichenhan D; Bottcher LM; Toth R; Hendriksen JD; Koop C; Lutsik P; Matzk S; Warnatz HJ; Amstislavskiy V; Feuerstein C; Raeder B; Bogatyrova O; Schmitz EM; Hube-Magg C; Kluth M; Huland H; Graefen M; Lawerenz C; Henry GH; Yamaguchi TN; Malewska A; Meiners J; Schilling D; Reisinger E; Eils R; Schlesner M; Strand DW; Bristow Robert G; Boutros PC; von KC; Gordenin D; Sultmann H; Brors B; Sauter G; Plass C; Yaspo ML; Korbel JO; Schlomm T; Weischenfeldt J; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany (2018)
    Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ?55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples.

View more