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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
Metabolomics informs common patterns of molecular dysfunction across histologies of renal cell carcinoma
Renzo G DiNatale1, Alejandro Sanchez2, A Ari Hakimi1
1Urology Department, Memorial Sloan Kettering Cancer Center, New York, NY; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract:
The last 30 years of research in renal cell carcinoma (RCC) has revealed that the vast majority of RCC histologies share a recurrent pattern of mutations to metabolic genes, including VHL, MTOR, ELOC, TSC1/2, FH, SDH, and mitochondrial DNA. This has prompted intense study of the consequences of these mutations on cellular metabolism and physiology in vivo by leveraging high-throughput technologies to measure small-molecule metabolites (i.e., metabolomics). The purpose of this review is to give a broad and integrated view on the discoveries made in RCC with metabolomics, and to give a basic understanding of the experimental design of metabolomic studies. Our discussion is organized around five concepts which synthesize discoveries from genomics and metabolomics into the molecular basis of RCC and transcend the different RCC histologies: (1) metabolic phenotypes unique to certain genotypes, (2) mitochondrial dysfunction, (3) the oxidative stress response, (4) epigenetics, and (5) therapy targeted to metabolism. We conclude by proposing several promising lines of investigation that intersect metabolism with emerging ideas in RCC biology.
Insights
Renal cell carcinoma (RCC) research shows common metabolic gene mutations. Metabolomics reveals how these genetic changes impact cancer cell metabolism, offering new therapeutic targets.
Area of Science:
- Oncology
- Metabolomics
- Genetics
Background:
- Renal cell carcinoma (RCC) exhibits recurrent mutations in metabolic genes across various histologies.
- These mutations in genes like VHL, MTOR, and FH affect cellular metabolism and physiology.
- Metabolomics has become crucial for studying these metabolic alterations in vivo.
Purpose of the Study:
- To provide an integrated overview of metabolomics discoveries in RCC.
- To explain the experimental design of metabolomic studies in the context of RCC.
- To synthesize genomics and metabolomics findings into the molecular basis of RCC.
Main Methods:
- Leveraging high-throughput technologies for metabolite measurement (metabolomics).
- Integrating genomic data with metabolomic profiles.
- Analyzing five key concepts linking genotype to metabolic phenotype in RCC.
Main Results:
- Identification of genotype-specific metabolic phenotypes in RCC.
- Understanding the role of mitochondrial dysfunction in RCC metabolism.
- Characterization of the oxidative stress response and epigenetic alterations in RCC.
Conclusions:
- Metabolomics provides critical insights into the molecular underpinnings of RCC.
- Metabolic alterations are a unifying feature across different RCC histologies.
- Targeting metabolism presents a promising therapeutic strategy for RCC, with future research directions identified.
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