Methodology article

Estimation of tumor heterogeneity using CGH array data

Kai Wang^1,2 , Jian Li¹ , Shengting Li¹ , Lars Bolund¹ and Carsten Wiuf²

¹Institute of Human Genetics, University of Aarhus, Aarhus, Denmark

²BiRC – Bioinformatics Research Center, University of Aarhus, Aarhus, Denmark

author email corresponding author email

BMC Bioinformatics 2009, 10:12doi:10.1186/1471-2105-10-12

Published:	9 January 2009

Abstract

Background

Array-based comparative genomic hybridization (CGH) is a commonly-used approach to detect DNA copy number variation in whole genome-wide screens. Several statistical methods have been proposed to define genomic segments with different copy numbers in cancer tumors. However, most tumors are heterogeneous and show variation in DNA copy numbers across tumor cells. The challenge is to reveal the copy number profiles of the subpopulations in a tumor and to estimate the percentage of each subpopulation.

Results

We describe a relation between experimental data and exact DNA copy number and develop a statistical method to reveal the heterogeneity of tumors containing a mixture of different-stage cells. Furthermore, we validate the method on simulated data and apply the method to 29 pairs of breast primary tumors and their matched lymph node metastases.

Conclusion

We demonstrate a new method for CGH array analysis that allows a tumor sample to be classified according to its heterogeneity. The method gives an interpretable series of copy number profiles, one for each major subpopulation in a tumor. The profiles facilitate identification of copy number alterations in cancer development.