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PCR-based RFLP screening of the commonly deleted 3p loci in renal cortical neoplasms
A K el-Naggar1, J G Batsakis, G Wang
1Department of Pathology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Abstract:
Cytogenetic deletions and loss of heterozygosity (LOH) at certain restriction fragment length polymorphic (RFLP) loci on the short arm of chromosome 3 occur in most nonpapillary clear cell variants of renal cell carcinoma (RCC). Studies of other variants of renal cell carcinomas are sparse and inconclusive. We investigated the LOH at three of the most commonly deleted loci on the short arm of chromosome 3 in 50 neoplasms representing the histopathologic spectrum of renal cortical neoplasms by polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay and Southern blotting analysis. Our results indicate that PCR-based RFLP analysis accurately identified the LOH on the short arm of chromosome 3 in the different histopathologic variants of renal neoplasms. LOH was observed at D3F15S2 locus (3p21 telomeric) in > 60% of nonpapillary renal cell carcinomas. In contrast, 1 of 6 papillary renal cell carcinomas showed LOH at D3S32 locus (3p21 centromeric), and one of seven oncocytomas demonstrated LOH at D3F15S2 locus. We also report that 1 of 3 collecting duct carcinomas showed LOH at D3S32 locus. In this series there was no correlation between LOH, histologic grade, tumor stage, and DNA content. We conclude that (a) LOH on 3p is not restricted to the clear cell type of RCC, (b) the most common LOH were telomeric to D3S32 locus at the 3p21 region, and (c) no statistical correlation between the LOH at 3p and histologic grade, DNA ploidy, or clinical stage was found in this series.
Insights
Loss of heterozygosity (LOH) on chromosome 3p occurs in various renal neoplasms, not just clear cell renal cell carcinoma (RCC). This study found LOH at 3p21 in over 60% of nonpapillary RCCs, suggesting broader implications for renal tumor genetics.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Cytogenetic deletions and loss of heterozygosity (LOH) at chromosome 3p are common in clear cell renal cell carcinoma (RCC).
- Limited data exists on LOH in other renal neoplasm subtypes.
- Investigating LOH across the histopathologic spectrum of renal cortical neoplasms is crucial.
Purpose of the Study:
- To investigate LOH at commonly deleted loci on chromosome 3p in a diverse set of 50 renal cortical neoplasms.
- To determine if LOH on 3p is exclusive to nonpapillary clear cell RCC.
- To correlate LOH findings with histopathologic subtype, grade, stage, and DNA content.
Main Methods:
- Utilized polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay.
- Employed Southern blotting analysis for confirmation.
- Analyzed 50 neoplasms representing various renal cortical histopathologic subtypes.
Main Results:
- PCR-based RFLP accurately identified LOH on chromosome 3p across different renal neoplasm variants.
- LOH at D3F15S2 (3p21 telomeric) was observed in over 60% of nonpapillary RCCs.
- LOH was also detected in a minority of papillary RCCs (D3S32), oncocytomas (D3F15S2), and collecting duct carcinomas (D3S32).
Conclusions:
- LOH on chromosome 3p is not restricted to clear cell RCC and occurs in other renal neoplasms.
- The most frequent LOH events were telomeric to the D3S32 locus within the 3p21 region.
- No statistical correlation was found between 3p LOH and histologic grade, DNA ploidy, or clinical stage in this series.