2446–2456 Nucleic Acids Research, 2008, Vol. 36, No. 7 doi:10.1093/nar/gkn089 Published online 27 February 2008 SNP panel identification assay (SPIA): a genetic-based assay for the identification of cell lines Francesca Demichelis1,2,*, Heidi Greulich2,3,4, Jill A. Macoska 5 , Rameen Beroukhim2,3,4, William R. Sellers2,3,4, Levi Garraway2,3,4 and Mark A. Rubin1,2,4 1Department of Pathology, Brigham and Women’s Hospital, 2Harvard Medical School, 3Department of Medical Oncology and Center for Cancer Genome Discovery, Dana Farber Cancer Institute, Boston, MA, 4Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA and 5Department of Urology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI USA Received December 26, 2007; Revised February 10, 2008; Accepted February 11, 2008 ABSTRACT Translational research hinges on the ability to make observations in model systems and to implement those findings into clinical applications, such as the development of diagnostic tools or targeted ther- apeutics. Tumor cell lines are commonly used to model carcinogenesis. The same tumor cell line can be simultaneously studied in multiple research laboratories throughout the world, theoretically generating results that are directly comparable. One important assumption in this paradigm is that researchers are working with the same cells. However, recent work using high throughput geno- mic analyses questions the accuracy of this assumption. Observations by our group and others suggest that experiments reported in the scientific literature may contain pre-analytic errors due to inaccurate identities of the cell lines employed. To address this problem, we developed a simple approach that enables an accurate determination of cell line identity by genotyping 34 single nucleo- tide polymorphisms (SNPs). Here, we describe the empirical development of a SNP panel identification assay (SPIA) compatible with routine use in the laboratory setting to ensure the identity of tumor cell lines and human tumor samples throughout the course of long term research use. INTRODUCTION The recognition that cancer is a genomic disease has prompted signiﬁcant eﬀorts to characterize large numbers of human tumor samples. For example, a pilot project called The Cancer Genome Altas (TCGA) has begun to sequence thousands of samples from three common tumor types (i.e. brain (glioblastoma multiforme), lung (squa- mous carcinoma) and ovarian (serous cystadenocarci- noma)) with a long-term goal of comprehensive human cancer genome characterization (National Human Genome Research Institute, http://www.genome.gov). Discoveries in human tumor samples will pave the road in our understanding of commonly altered gene pathways and lead to pre-clinical studies to address the biologic signiﬁcance of these newly identiﬁed mutations, ampliﬁca- tions and deletions. Pre-clinical, functional studies are often conducted in tumor cell lines as model systems for understanding perturbations in primary human tumors. In addition to functional studies, cell lines are now important in the identiﬁcation of therapeutic targets and in the under- standing of molecular pathways related to drug–tumor interactions as recently demonstrated by Lamb et al. (1). A MedLine search of ‘cell line’ and ‘cancer human’ identiﬁed 96 758 articles where human cell lines have been employed to study cancer biology. Bio-resource centers preserve and sell human cell lines. For example, the American Type Culture Collection (ATCC, http:// www.lgcpromochem-atcc.com/) provides researchers with a collection of 700 human cancer cell lines. Commonly, cell lines are transferred extensively between investigators and institutes, and may be cultivated over prolonged periods of time. One well-recognized risk in cell line maintenance is human error, either by mislabeling or cross-contamination, the latter ultimately resulting in *To whom correspondence should be addressed. Tel: +1 646 962 5616; Fax: +1 212 746 8816; Email: frd2004@med.cornell.edu 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.