title: DeconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution.
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.
authors.affiliation: 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.|UCL Cancer Institute, Bill Lyons Informatics Centre, Paul O'Gorman Building, Huntley Street, London, WC1E 6DD, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rosenthal
authors.affiliation: 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.
authors.forename: Nicholas
authors.initials: N
authors.lastname: McGranahan
authors.affiliation: UCL Cancer Institute, Bill Lyons Informatics Centre, Paul O'Gorman Building, Huntley Street, London, WC1E 6DD, UK. javier.herrero@ucl.ac.uk.
authors.forename: Javier
authors.initials: J
authors.lastname: Herrero
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. taylorb@mskcc.org.|Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. taylorb@mskcc.org.|Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. taylorb@mskcc.org.
authors.forename: Barry S
authors.initials: BS
authors.lastname: Taylor
authors.affiliation: UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, Paul O'Gorman Building, Huntley Street, London, WC1E 6DD, UK. charles.swanton@crick.ac.uk.|The Francis Crick Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK. charles.swanton@crick.ac.uk.
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D003564:Cytidine Deaminase / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D015894:Genome, Human; D006801:Humans; D009154:Mutation / Q000235:genetics
chemical_list: D003564:Cytidine Deaminase