Differences in mutations across tumour sizes in clear-cell renal cell carcinoma

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Updated: Jun 13, 2025

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
05:36

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

8.9K

Steven M Monda1,2, Benjamin W Carney2, Allison M May3

  • 1Department of Urologic Surgery, UC Davis, Sacramento, CA, USA.

BJU International
|September 12, 2024
PubMed
Abstract

Insights

Clear-cell renal cell carcinoma (ccRCC) shows genomic differences based on tumour size. Aggressive mutations like SETD2, BAP1, and CDKN2A loss are more common in larger ccRCCs but still impact smaller tumours.

Area of Science:

  • Oncology
  • Genetics
  • Genomic Medicine

Background:

  • Clear-cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype.
  • Tumour size is a known prognostic factor in ccRCC.
  • Understanding the genomic landscape of ccRCC relative to tumour size is crucial for targeted therapies.

Purpose of the Study:

  • To investigate the association between tumour size and the distribution of key mutations (VHL, PBRM1, SETD2, BAP1, CDKN2A loss) in ccRCC.
  • To evaluate the prognostic significance of aggressive mutations in smaller ccRCCs (≤7 cm).

Main Methods:

  • Analysis of mutation data from 1039 ccRCC patients across TRACERx, TCGA, and CAGEKID cohorts.
  • Logistic regression modeling to correlate mutation presence with tumour size.
  • Survival and metastasis analyses for aggressive mutations in tumours ≤7 cm, controlling for tumour size.

Main Results:

  • Tumour size was positively associated with aggressive mutations SETD2, BAP1, and CDKN2A loss (P<0.001).
  • VHL showed a mild negative association with size (P=0.01), while PBRM1 showed no significant association.
  • In ccRCCs ≤7 cm, SETD2 and CDKN2A loss correlated with metastatic disease (ORs ~3.86, P<0.05) and CDKN2A loss with worse overall survival (HR 2.19, P=0.03).

Conclusions:

  • ccRCC exhibits distinct genomic profiles based on tumour size.
  • Aggressive mutations are less frequent in small ccRCCs but retain prognostic significance for metastasis, survival, and recurrence.
  • These findings highlight the importance of molecular profiling even in smaller ccRCCs.
Keywords:
bap1cdkn2aclear‐cell renal cell carcinomagenomicsrenal cell carcinomasetd2survivaltcgatracerxtumour size

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