title: Sample type bias in the analysis of cancer genomes.
abstract: There is widespread agreement that cancer gene discovery requires high-quality tumor samples. However, whether primary tumors or cultured samples are superior for cancer genomics has been a longstanding subject of debate. This debate has recently become more important because federally funded cancer genomics has been centralized under The Cancer Genome Atlas, which has chosen to focus exclusively on primary tumors. Here, we provide a data-driven "perspective" on the effect of sample type selection on cancer genomics research. We show that, in the case of glioblastoma multiforme, primary tumors and xenografts are best for the identification of amplifications, whereas xenografts and cell lines are superior for the identification of homozygous deletions. We also note that many of the most important oncogenes and tumor suppressor genes have been discovered through the use of cell lines and xenografts, and highlight the lack of published evidence supporting the dogma that ex vivo culture generates artifactual genetic lesions. Based on this analysis, we suggest that cancer genomics projects such as The Cancer Genome Atlas should include a variety of sample types such as xenografts and cell lines in their integrated genomic analysis of cancer.
authors: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia 20057, USA.
authors: David A
authors: DA
authors: Solomon
authors: Jung-Sik
authors: JS
authors: Kim
authors: Habtom W
authors: HW
authors: Ressom
authors: Zita
authors: Z
authors: Sibenaller
authors: Timothy
authors: T
authors: Ryken
authors: Walter
authors: W
authors: Jean
authors: Darell
authors: D
authors: Bigner
authors: Hai
authors: H
authors: Yan
authors: Todd
authors: T
authors: Waldman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005784:Gene Amplification; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D023281:Genomics / Q000379:methods* / Q000592:standards; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D023041:Xenograft Model Antitumor Assays