The Genomics & Bioinformatics Group (GBG) is undertaking what has been characterized by others as a forerunner of the NCI/NHGRI Human Genome Atlas project (TCGA). Whereas TCGA aims at molecular profiling of clinical tumors at the DNA, RNA, and chromosomal levels, the GBGs work aims at a broader profiling at the DNA, RNA, protein, chromosomal, functional, and pharmacological levels but in the logistically simpler, more homogeneous, more reproducible context of human cell lines, rather than clinical tumors. More specifically, we have established a set of collaborations for molecular profiling of selected drug-resistant cell lines and also the panel of 60 human cancer cell lines (the NCI-60) used by the NCI Developmental Therapeutics Program to screen >100,000 compounds and natural products for anticancer activity. The ultimate aim is to discover new drugs and biomarkers for targeted, personalized treatment of cancer. In that aim, we are also setting the table for other researchers by producing molecular profile databases and bioinformatic software tools that are being used by thousands of laboratories around the world. That is, we are providing infrastructure for post-genomic biomedical research at the same time as we are pursuing translational goals related to drugs and biomarkers for personalization of cancer therapy. That enterprise yields a number of types of contributions: Molecular profile databases used by large numbers of laboratories and investigators (4 of our publications presenting the data have each generated >400 literature citations to date). Bioinformatic computer tools and resources (the Miner Suite) that we originally programmed because we needed them but that we also make freely available on our web site (http://discover.nci.nih.gov). The manuscript on one of those tools (GoMiner) has been cited in the literature almost 300 times. Translationally significant results derived from a combination of integromic molecular profiling studies and the bioinformatic developments. Five of those findings with clinical implications have been (i) biomarkers to distinguish colon from ovarian tumors of unknown origin, (ii) asparagine synthetase as a predictor of ovarian cancer cell response to L-asparaginase; (iii) the Permissive-Apoptosis Resistance (PAR) two-step model for development of acquired drug resistance; (iv) MDR1-inverse compounds more active in cancer cells that express MDR1; (v) critical evidence in the 1990s that led to clinical development of oxaliplatin, now a standard-of-care agent for treatment of colon cancer.
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