Molecular and Clinicopathological Profiling of Clear Cell Renal Cell Carcinoma with Rhabdoid Features: An Integrative...

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Clear cell renal cell carcinoma with rhabdoid features (ccRCC-R) is an aggressive subtype of kidney cancer.
• ccRCC-R presents a poor prognosis and limited therapeutic strategies.

Purpose of the Study:

• To define the clinicopathologic and molecular characteristics of ccRCC-R.
• To identify potential therapeutic vulnerabilities and guide precision oncology.

Main Methods:

• Integrated analysis of 17 ccRCC-R tumors using histomorphology, immunohistochemistry, and targeted next-generation sequencing (NGS).
• Unsupervised hierarchical clustering based on pathway-specific somatic mutations.

Main Results:

• ccRCC-R exhibits diverse architectural patterns and immunohistochemical profiles, including loss of PAX8 and Claudin4.
• Frequent loss of SMARCA2 with retained SMARCA4 suggests chromatin remodeling aberrations.
• Four molecular subgroups were identified based on alterations in DNA damage repair, chromatin remodeling, PI3K/AKT/mTOR, and MAPK pathways.

Conclusions:

• ccRCC-R is molecularly heterogeneous, necessitating pathway-based stratification.
• Findings support precision oncology approaches and biomarker-informed clinical trial design for ccRCC-R.