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Intra-tumor heterogeneity concerns the existence of genetically different subclones within the same tumor. Single sample quantification of heterogeneity relies on precise determination of chromosomal copy numbers throughout the genome, and an assessment of whether identified mutation variant allele fractions match clonal or subclonal copy numbers. We discuss these issues using data from SNP arrays, whole exome sequencing and pathologist purity estimates on several breast cancers characterized by ERBB2 amplification. We show that chromosomal copy numbers can only be estimated from SNP array signals or sequencing depths for subclonal tumor samples with simple subclonal architectures under certain assumptions.   Electronic supplementary material  The online version of this article (doi:10.1186/s13059-014-0470-7) contains supplementary material, which is available to authorized users.

Deciphering clonality in aneuploid breast tumors using SNP array and sequencing data