Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity

Markus Rasmussen,Helgi Birgisson,Bengt Glimelius,Hanna Kultima,Magnus Sundström,Johan Botling,Anders Isaksson,Patrick Micke

doi:10.1186/gb-2011-12-10-r108

Abstract

We describe a bioinformatic tool, Tumor Aberration Prediction Suite (TAPS), for the identification of allele-specific copy numbers in tumor samples using data from Affymetrix SNP arrays. It includes detailed visualization of genomic segment characteristics and iterative pattern recognition for copy number identification, and does not require patient-matched normal samples. TAPS can be used to identify chromosomal aberrations with high sensitivity even when the proportion of tumor cells is as low as 30%. Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors.

Highlights

A characteristic feature of cancer cells is that their genomic DNA is altered [1]
Tumor Aberration Prediction Suite We present a tool and algorithm for allele-specific copy number analysis of tumor samples on Affymetrix 500 K and single nucleotide polymorphism (SNP) 6.0 arrays called Tumor Aberration Prediction Suite (TAPS)
We describe allele-specific copy number profiling of 7 lung cancer cell lines and 12 colon tumor samples, partially validated through spectral karyotyping (SKY) and DNA ploidy analysis

Summary

Background

A characteristic feature of cancer cells is that their genomic DNA is altered [1]. Tumor cells frequently contain a wide range of aberrations, with gains, losses and translocations of genetic material often affecting a majority of the genome. This works well for detecting aberrations in diploid non-cancer samples as the normalized intensity of copy number two should coincide for query and reference data It may work reasonably well on tumors that have few and relatively small genomic aberrations. Tumor Aberration Prediction Suite We present a tool and algorithm for allele-specific copy number analysis of tumor samples on Affymetrix 500 K and SNP 6.0 arrays called Tumor Aberration Prediction Suite (TAPS). It handles samples with aneuploidy and the presence of normal cells and facilitates detection of tumor cell heterogeneity. We describe allele-specific copy number profiling of 7 lung cancer cell lines and 12 colon tumor samples, partially validated through spectral karyotyping (SKY) and DNA ploidy analysis

Results and discussion

Limitations

Conclusions

Materials and methods