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

Genome Biol. 2016 Feb 22:17:31. doi: 10.1186/s13059-016-0893-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cytidine Deaminase / genetics
  • DNA Mutational Analysis
  • DNA Repair / genetics*
  • DNA Repair-Deficiency Disorders / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Genome, Human
  • Humans
  • Mutation / genetics


  • Cytidine Deaminase

Supplementary concepts

  • Adenocarcinoma Of Esophagus