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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and
Christina A Von Roemeling1, Laura A Marlow1, Derek C Radisky1
1Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida.
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.
Insights
Researchers identified new genes driving clear cell renal cell carcinoma (ccRCC) progression. This study reveals novel therapeutic targets and biomarkers for advanced ccRCC, offering hope for improved patient outcomes.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Advanced clear cell renal cell carcinoma (ccRCC) lacks effective targeted therapies for long-term disease management.
- Understanding the genetic factors driving tumor initiation and progression is crucial for developing new treatments.
Purpose of the Study:
- To identify novel genes and pathways involved in clear cell renal cell carcinoma (ccRCC) tumorigenesis.
- To discover potential therapeutic targets and biomarkers for advanced ccRCC.
Main Methods:
- High-throughput genetic analysis of patient ccRCC tissues to identify overexpressed transcripts.
- High-throughput lentivirus screening of 195 overexpressed genes in ccRCC cell lines to assess proliferative impact.
- Functional characterization of identified genes in tumor cell invasion.
Main Results:
- Gene array analysis revealed transcripts consistently elevated in ccRCC compared to normal renal tissues.
- A lentivirus screen identified 31 "hits" (genes) that significantly contribute to ccRCC cell proliferation.
- Several identified genes are novel to ccRCC and cancer biology, with some implicated in tumor invasion.
Conclusions:
- The study uncovers critical pathways involved in ccRCC tumorigenicity.
- Novel candidate factors have been identified for potential therapeutic intervention in ccRCC.
- These findings suggest new diagnostic or prognostic biomarkers for advanced ccRCC patients.
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