Topological Analysis of Amplicon Structure in Comparative Genomic Hybridization (CGH) Data: An Application to ERBB2/HER2/NEU Amplified Tumors
DNA copy number aberrations (CNAs) play an important role in cancer and can be experimentally detected using microarray comparative genomic hybridization (CGH) techniques. Amplicons, CNAs that extend over large sections of the genome, are difficult to study since they may contain multiple independent and dependent copy number changes. Here, we propose an algorithm to find the CNAs structure within a given amplicon. Our method relies on the observation that co-occurring CNAs can be encoded as 1-dimensional cycles. Applying this method to breast cancer patients known as ERBB2/HER2/NEU amplified we find three regions that can be co-occuring: the first region is in the cytoband 17q12, where the ERBB2 gene is located, the second region expands between 17q21.2 to 17q21.31 and includes the keratin genes, the third one is 17q21.33. We suggest that the first homology group helps uncovering the structure of amplicons.
KeywordsCopy number aberrations Cancer Computational homology First homology group
We would like to thank H. Bengtsson and T. Speed for very helpful comments during the development of this methodology. T.B and J.A. were partially supported by NSF grant 1217324 and by NIH-RIMI (Research Infrastructure in Minority Institutions) grant 2P20MD000544-06. SA was partially supported by the Ministerio de Economía y competitividad grant MTM2013-42486-P.
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