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Distinct patterns of chromosomal losses in clinically synchronous and asynchronous bilateral renal cell carcinoma
Hiroki Kito1, Hiroshi Suzuki, Tatsou Igarashi
1Department of Urology, Graduate School of Medicine, Chiba University, Japan.
Purpose:
Bilateral renal cell carcinoma has been reported to occur in 1% to 4% of patients with renal cancer. However, whether bilateral renal cell carcinoma involves metastatic lesions of the contralateral kidney or develops as simultaneous primary tumors remains unclear to date. Thus, we investigated chromosomal losses and von Hippel-Lindau (VHL) gene abnormalities in bilateral tumors from patients with nonfamilial bilateral renal cell carcinoma.
Materials And Methods:
Genomic DNA was exacted from 2 tumors in 8 patients each with nonfamilial bilateral renal cell carcinoma, including clinically asynchronous and synchronous disease in 5 and 3, respectively. The DNA was then subjected to microsatellite analysis on 13 chromosomal loci. In addition, polymerase chain reaction-single nucleotide specific conformation polymorphism analysis and direct sequencing of 3 exons of the VHL gene were performed.
Results:
All 5 asynchronous cases showed loss of the same allele in bilateral tumors, indicating a common clonal origin. In contrast, 2 of the 3 synchronous cases showed different patterns of chromosomal loss in the right and left renal tumors, suggesting bilateral primary origins. The other synchronous case with loss of the same allele in each tumor involved right stage T3b and left stage T1a neoplasms. No VHL gene mutations were detected in any case.
Conclusions:
Except for a small number of cases synchronous and asynchronous bilateral renal cell carcinoma may represent the simultaneous appearance of separate primary tumors and metastatic progression from the contralateral kidney, respectively.
Insights
Bilateral renal cell carcinoma can arise from separate primary tumors or metastasis. Asynchronous tumors often share a common origin, while synchronous tumors may be distinct primary growths.
Area of Science:
- Oncology
- Genetics
- Urology
Background:
- Bilateral renal cell carcinoma (BRCC) occurs in 1-4% of renal cancer patients.
- The origin of BRCC (metastasis vs. primary tumors) remains unclear.
Purpose of the Study:
- Investigate chromosomal losses and VHL gene in nonfamilial BRCC.
- Determine if BRCC involves metastatic lesions or simultaneous primary tumors.
Main Methods:
- Analyzed genomic DNA from bilateral tumors in 8 nonfamilial BRCC patients.
- Utilized microsatellite analysis and VHL gene sequencing.
- Examined both synchronous and asynchronous tumor presentations.
Main Results:
- Asynchronous BRCC cases showed common clonal origin (same allele loss).
- Synchronous BRCC cases often displayed different chromosomal loss patterns, suggesting separate origins.
- No VHL gene mutations were detected in any of the studied cases.
Conclusions:
- BRCC can represent distinct primary tumors or contralateral metastasis.
- Asynchronous BRCC typically indicates metastasis, while synchronous BRCC may indicate separate primary origins.