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Updated: Dec 2, 2025
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Clear cell renal cell carcinoma ontogeny and mechanisms of lethality
Eric Jonasch1, Cheryl Lyn Walker2, W Kimryn Rathmell3
1Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ejonasch@mdanderson.org.
Abstract:
The molecular features that define clear cell renal cell carcinoma (ccRCC) initiation and progression are being increasingly defined. The TRACERx Renal studies and others that have described the interaction between tumour genomics and remodelling of the tumour microenvironment provide important new insights into the molecular drivers underlying ccRCC ontogeny and progression. Our understanding of common genomic and chromosomal copy number abnormalities in ccRCC, including chromosome 3p loss, provides a mechanistic framework with which to organize these abnormalities into those that drive tumour initiation events, those that drive tumour progression and those that confer lethality. Truncal mutations in ccRCC, including those in VHL, SET2, PBRM1 and BAP1, may engender genomic instability and promote defects in DNA repair pathways. The molecular features that arise from these defects enable categorization of ccRCC into clinically and therapeutically relevant subtypes. Consideration of the interaction of these subtypes with the tumour microenvironment reveals that specific mutations seem to modulate immune cell populations in ccRCC tumours. These findings present opportunities for disease prevention, early detection, prognostication and treatment.
Insights
Clear cell renal cell carcinoma (ccRCC) progression is linked to genomic alterations and tumor microenvironment interactions. Understanding these molecular features aids in ccRCC subtype classification for improved treatment strategies.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Clear cell renal cell carcinoma (ccRCC) molecular features are increasingly understood.
- Studies like TRACERx Renal highlight tumor genomics and microenvironment interactions in ccRCC.
- Genomic and chromosomal abnormalities, such as chromosome 3p loss, are key in ccRCC.
Purpose of the Study:
- To define molecular features driving ccRCC initiation and progression.
- To categorize ccRCC based on molecular defects and their clinical relevance.
- To explore the interplay between ccRCC subtypes and the tumor microenvironment.
Main Methods:
- Analysis of tumor genomics and chromosomal copy number abnormalities.
- Identification of truncal mutations (VHL, SET2, PBRM1, BAP1) in ccRCC.
- Investigation of molecular defects and their impact on DNA repair pathways.
Main Results:
- Genomic abnormalities are classified into those driving initiation, progression, or lethality.
- Truncal mutations contribute to genomic instability and DNA repair defects.
- Specific mutations modulate immune cell populations within ccRCC tumors.
Conclusions:
- Molecular categorization of ccRCC into clinically relevant subtypes is possible.
- Tumor microenvironment interactions are influenced by specific ccRCC mutations.
- These findings offer new avenues for ccRCC prevention, detection, prognostication, and treatment.
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