A general framework for analyzing tumor subclonality using SNP array and DNA sequencing data

Genome Biol. 2014 Sep 25;15(9):473. doi: 10.1186/s13059-014-0473-4.


Intra-tumor heterogeneity reflects cancer genome evolution and provides key information for diagnosis and treatment. When bulk tumor tissues are profiled for somatic copy number alterations (sCNA) and point mutations, it may be difficult to estimate their cellular fractions when a mutation falls within a sCNA. We present the Clonal Heterogeneity Analysis Tool, which estimates cellular fractions for both sCNAs and mutations, and uses their distributions to inform macroscopic clonal architecture. In a set of approximately 700 breast tumors, more than half appear to contain multiple recognizable aneuploid tumor clones, and many show subtype-specific differences in clonality for known cancer genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Lineage
  • Female
  • Gene Frequency
  • Genetic Heterogeneity
  • Humans
  • Loss of Heterozygosity
  • Models, Genetic
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA*
  • Software*