Physical and functional mapping of a tumor suppressor locus for renal Cell carcinoma within chromosome 3p12

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 chromo...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-08, Vol.58 (16), p.3533-3537
Main Authors: LOTT, S. T, LOVELL, M, NAYLOR, S. L, KILLARY, A. M
Format: Article
Language:English
Subjects:
Acid Anhydride Hydrolases
Biological and medical sciences
Carcinoma, Renal Cell - genetics
Chromosome Mapping
Chromosomes, Human, Pair 3 - genetics
Genes, Tumor Suppressor - genetics
Humans
Kidney Neoplasms - genetics
Kidneys
Medical sciences
Microsatellite Repeats - genetics
Mitogen-Activated Protein Kinase Kinases
Neoplasm Proteins - genetics
Nephrology. Urinary tract diseases
Protein Kinases - genetics
Proteins - genetics
Translocation, Genetic
Tumors of the urinary system
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0008-5472
1538-7445