For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
45
views
11
references
 Top references
cited by
390
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      44
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Analysis of somatic mutations provides insight into the mutational processes that have shaped the cancer genome, but such analysis currently requires large cohorts. We develop deconstructSigs, which allows the identification of mutational signatures within a single tumor sample.

          Results

          Application of deconstructSigs identifies samples with DNA repair deficiencies and reveals distinct and dynamic mutational processes molding the cancer genome in esophageal adenocarcinoma compared to squamous cell carcinomas.

          Conclusions

          deconstructSigs confers the ability to define mutational processes driven by environmental exposures, DNA repair abnormalities, and mutagenic processes in individual tumors with implications for precision cancer medicine.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13059-016-0893-4) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references11

          • Record: found
          • Abstract: found
          • Article: not found

          Signatures of mutational processes in human cancer

          Ludmil Alexandrov, Serena Nik-Zainal, David Wedge … (2015)
          All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy.
          Article 0 comments Cited 2265 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Reshaping Data with thereshapePackage

            Hadley Wickham (2007)
            Article 0 comments Cited 415 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Microsatellite instability in colorectal cancer.

              C. Boland, Ajay Goel (2010)
              Microsatellite instability (MSI) is a hypermutable phenotype caused by the loss of DNA mismatch repair activity. MSI is detected in about 15% of all colorectal cancers; 3% are of these are associated with Lynch syndrome and the other 12% are caused by sporadic, acquired hypermethylation of the promoter of the MLH1 gene, which occurs in tumors with the CpG island methylator phenotype. Colorectal tumors with MSI have distinctive features, including a tendency to arise in the proximal colon, lymphocytic infiltrate, and a poorly differentiated, mucinous or signet ring appearance. They have a slightly better prognosis than colorectal tumors without MSI and do not have the same response to chemotherapeutics. Discovery of MSI in colorectal tumors has increased awareness of the diversity of colorectal cancers and implications for specialized management of patients.
              Article 0 comments Cited 410 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Javier Herrero: javier.herrero@ucl.ac.uk
                Barry S. Taylor: taylorb@mskcc.org
                Charles Swanton: charles.swanton@crick.ac.uk
                Journal
                Journal ID (nlm-ta): Genome Biol
                Journal ID (iso-abbrev): Genome Biol
                Title: Genome Biology
                Publisher: BioMed Central (London )
                ISSN (Print): 1474-7596
                ISSN (Electronic): 1474-760X
                Publication date (Electronic): 22 February 2016
                Publication date PMC-release: 22 February 2016
                Publication date Collection: 2016
                Volume: 17
                Electronic Location Identifier: 31
                Affiliations
                [ ]UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, Paul O’Gorman Building, Huntley Street, London, WC1E 6DD UK
                [ ]The Francis Crick Institute, 44 Lincoln’s Inn Fields, London, WC2A 3LY UK
                [ ]Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London, London, WC1E 6BT UK
                [ ]UCL Cancer Institute, Bill Lyons Informatics Centre, Paul O’Gorman Building, Huntley Street, London, WC1E 6DD UK
                [ ]Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY USA
                [ ]Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY USA
                [ ]Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY USA
                Article
                Publisher ID: 893
                DOI: 10.1186/s13059-016-0893-4
                PMC ID: 4762164
                PubMed ID: 26899170
                SO-VID: d6f10631-0789-493e-b675-e9145f428c70
                Copyright © © Rosenthal et al. 2016
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 30 October 2015
                Date accepted : 4 February 2016
                Funding
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100000781, European Research Council;
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100000833, Rosetrees Trust;
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100000265, Medical Research Council;
                Funded by: Cancer Research United Kingdom
                Funded by: FundRef http://dx.doi.org/10.13039/501100000329, Novo Nordisk UK Research Foundation;
                Award ID: 16584
                Award Recipient :
                Categories
                Subject: Software
                Custom metadata
                issue-copyright-statement © The Author(s) 2016

                ScienceOpen disciplines: Genetics
                Keywords: mutational signatures,esophageal carcinoma,apobec,single samples
                Data availability:
                ScienceOpen disciplines: Genetics
                Keywords: mutational signatures, esophageal carcinoma, apobec, single samples

                Comments

                Comment on this article

                scite_

                Similar content44

                See all similar

                Cited by553

                See all cited by

                Most referenced authors322

                See all reference authors