Journal article

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

Ingrid M Loennstedt, Franco Caramia, Jason Li, Debora Fumagalli, Roberto Salgado, Andrew Rowan, Max Salm, Nnennaya Kanu, Peter Savas, Stuart Horswell, Stephan Gade, Sibylle Loibl, Patrick Neven, Christos Sotiriou, Charles Swanton, Sherene Loi, Terence P Speed

GENOME BIOLOGY | BMC | Published : 2014


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 cert..

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Awarded by European Union

Awarded by Cancer Research UK

Awarded by Medical Research Council

Funding Acknowledgements

We thank Henrik Bengtsson at University of California, San Fransisco, USA and Pierre Neuvial, CNRS, France for useful discussions on BAF bias, and Henrik also for advice on using the aroma. affymetrix and PSCBS R packages. We also like to acknowledge Marcus Mayrhofer at Uppsala University, Sweden for introducing us to two dimensional patterns in SNP array data in the form of TAPS plots. This project was supported by European Union FP/project 'RESPONSIFY' No 278659. ShL was supported by Cancer Council Victoria. TPS was supported by NHMRC Australia Fellowship.