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Physical and Functional Mapping of a Tumor Suppressor Locus for Renal Cell Carcinoma within Chromosome 3p12¹

Division of Laboratory Medicine, Section of Experimental Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095 [S. T. L., M. L., A. M. K.], and Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284 [S. L. N.]

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.

¹ Supported by National Cancer Institute Grant R01 CA-62027 and the Marie 1. Morgan Fund for Kidney Cancer Research (to A. M. K.). S. T. L. was supported by National Cancer Institute Training Grant 5 T32 CA-09299-18.

² To whom requests for reprints should be addressed, at Division of Laboratory Medicine, Box 54, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4095. Phone: (713) 792-7835; Fax: (713) 745-0251; E-mail: sa95047@odin.mdacc.tmc.edu.

Received 2/ 4/98. Accepted 6/24/98.

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