title: Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration.
abstract: Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression. Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 'hits' that contribute to ccRCC cell proliferation. Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC.
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
authors: Christina A
authors: CA
authors: Von Roemeling
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
authors: Laura A
authors: LA
authors: Marlow
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
authors: Derek C
authors: DC
authors: Radisky
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
authors: Austin
authors: A
authors: Rohl
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
authors: Hege Ekeberg
authors: HE
authors: Larsen
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
authors: Johnny
authors: J
authors: Wei
authors: Incogen, Inc., Jacksonville, Florida.
authors: Heather
authors: H
authors: Sasinowska
authors: Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Jacksonville, Florida.
authors: Heng
authors: H
authors: Zhu
authors: MUSC Proteomics Center, Jacksonville, Florida.
authors: Richard
authors: R
authors: Drake
authors: Incogen, Inc., Jacksonville, Florida.
authors: Maciek
authors: M
authors: Sasinowski
authors: Division of Hematology and Oncology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
authors: Han W
authors: HW
authors: Tun
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
authors: John A
authors: JA
authors: Copland
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*