Related Experiment Videos
Physical and functional mapping of a tumor suppressor locus for renal cell carcinoma within chromosome 3p12
S T Lott1, M Lovell, S L Naylor
1Division of Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston 77030-4095, USA. sa95047@odin.mdacc.tmc.edu
Abstract:
Using a functional genetic approach, we previously identified a novel genetic locus, NRC-1 (Nonpapillary Renal Cell Carcinoma 1), that mediated tumor suppression and rapid cell death of renal cell carcinoma (RCC) cells in vivo. For these experiments, a defined subchromosomal fragment of human chromosome 3p was transferred into a sporadic RCC cell line via microcell fusion, and microcell hybrid clones were tested for tumorigenicity in vivo. The results indicated functional evidence for a novel tumor suppressor locus within the 3p14-p12 interval known to contain the most common fragile site of the human genome (FRA3B), the FHIT gene, and the breakpoint region associated with the familial form of RCC. We now report the physical mapping of the NRC-1 critical region by detailed microsatellite analyses of novel microcell hybrid clones containing transferred fragments of chromosome 3p in the RCC cell background that were phenotypically suppressed or unsuppressed for tumorigenicity in vivo. The results limit the region containing the tumor suppressor locus within chromosome 3p12. The FHIT gene, FRA3B, and the familial RCC breakpoint region were excluded from the NRC-1 critical region. Furthermore, the NRC-1 locus falls within a well-characterized homozygous deletion region of 5-7 Mb associated with a small cell lung carcinoma cell line, U2020, suggesting that a more general tumor suppressor gene may reside in this region.
Insights
Researchers identified a novel tumor suppressor locus, NRC-1, on chromosome 3p12 that causes renal cell carcinoma (RCC) cell death. This locus is distinct from FHIT and FRA3B, suggesting a new gene involved in RCC development.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- A novel genetic locus, NRC-1 (Nonpapillary Renal Cell Carcinoma 1), was previously identified as mediating tumor suppression and cell death in renal cell carcinoma (RCC) cells.
- Functional evidence suggested this locus resides within the 3p14-p12 region of human chromosome 3, a region known for common fragile sites (FRA3B) and the FHIT gene.
Purpose of the Study:
- To physically map the critical region of the NRC-1 tumor suppressor locus.
- To determine if the NRC-1 locus overlaps with FRA3B, the FHIT gene, or the familial RCC breakpoint region.
Main Methods:
- Utilized microcell fusion to transfer human chromosome 3p fragments into RCC cells.
- Analyzed novel microcell hybrid clones with suppressed or unsuppressed tumorigenicity using detailed microsatellite analyses.
- Physically mapped the NRC-1 critical region within chromosome 3p.
Main Results:
- The NRC-1 tumor suppressor locus was physically mapped to chromosome 3p12.
- The FHIT gene, FRA3B, and the familial RCC breakpoint region were excluded from the NRC-1 critical region.
- The NRC-1 locus is located within a 5-7 Mb homozygous deletion region associated with small cell lung carcinoma.
Conclusions:
- The NRC-1 locus represents a distinct tumor suppressor region on chromosome 3p12, separate from previously identified genes and regions associated with RCC.
- The NRC-1 locus's location within a homozygous deletion region suggests it may harbor a more generally acting tumor suppressor gene relevant to multiple cancer types.