Associating somatic mutations to clinical outcomes: a pan-cancer study of survival time

Genome Med. 2019 May 28;11(1):37. doi: 10.1186/s13073-019-0643-9.


We developed subclone multiplicity allocation and somatic heterogeneity (SMASH), a new statistical method for intra-tumor heterogeneity (ITH) inference. SMASH is tailored to the purpose of large-scale association studies with one tumor sample per patient. In a pan-cancer study of 14 cancer types, we studied the associations between survival time and ITH quantified by SMASH, together with other features of somatic mutations. Our results show that ITH is associated with survival time in several cancer types and its effect can be modified by other covariates, such as mutation burden. SMASH is available at .

Keywords: Copy number alteration; Intra-tumor heterogeneity; Somatic mutations; Subclone; Tumor mutation burden.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Clonal Evolution*
  • DNA, Neoplasm / genetics*
  • Genetic Heterogeneity*
  • Humans
  • Mutation Rate*
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Survival Analysis


  • Biomarkers, Tumor
  • DNA, Neoplasm