Comprehensive analysis of the genome transcriptome and proteome landscapes of three tumor cell lines

Human cancer cell lines have been an invaluable and practical resource for cancer research. The availability of genomic, transcriptomic and proteomic data on these lines is expected to further increase their utility. To this end, we conducted whole-genome and transcriptome sequencing on three tumor cell lines (A431, U251MG and U2OS) for which there is a large body of proteomics data [1]. The choice of these lines was also motivated by their origin from different lineages (tumor cell lines from mesenchymal, epithelial and glial tumors) and abundance of literature.A431 is used as a model cell line for epidermoid carcinoma and there are currently 3,359 publications describing studies using this cell line. It was established from an epidermoid carcinoma in the vulva of an 85-year-old patient [2]. This cell line expresses high levels of epidermal growth factor receptor (EGFR) and is often used to investigate cell proliferation and apoptosis. U251MG is a commonly used glioblastoma cell line (over 1,200 published articles) established from a male's brain tissue [3]. U2OS is an osteosarcoma cell line derived from a 15-year-old female [4]. Osteosarcoma tumors arise from cells of mesenchymal origin that differentiate to osteoblasts. It is the most common form of bone cancer, responsible for 2.4% of all malignancies in pediatric patients, and its triggers are currently not known [5]. U2OS is a common choice for osteosarcoma research: 35% of the articles associated with the osteosarcoma Medical Subject Headings (MeSH) term in the PubMed database have used this cell line.Using modern technologies, we subjected these three cell lines to genome and RNA sequencing in order to identify genomic alterations and expression of messenger and microRNAs. A review by Ideker and Sharan summarized studies that demonstrate how genes with a role in cancer tend to cluster together on well-connected sub-networks of protein-protein interactions [6]. We also earlier demonstrated that somatic mutati