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Localization of Tumor Suppressor Loci on Chromosome 9 in Primary Human Renal Cell Carcinomas¹

Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

To investigate the potential loss of tumor suppressor gene loci on chromosome 9 in human renal cell tumorigenesis we analyzed 42 paired normal and tumor DNAs with 18 polymorphic microsatellite markers spanning this chromosome. Fourteen of 42 (33%) tumors showed partial or complete deletion of chromosome 9. Deletion mapping provided evidence for the presence of a suppressor locus on both the short and long arm of chromosome 9. Homozygous deletion at 9p21–22 in one renal tumor and a selective deletion of distal 9q in another tumor localized the critical regions. The CDKN2/p16 gene was further investigated as a candidate suppressor locus on 9p21–22 by multiplex PCR, Southern analysis, and exon sequencing. We found no additional cases of homozygous deletion nor any rearrangements or point mutations of CDKN2/p16. This is the first report of 9p loss of heterozygosity, homozygous deletion of 9p21–22 and selective deletion of 9q in primary renal cell carcinomas. Understanding the molecular genetic basis of renal cell progression will require the isolation and characterization of additional tumor suppressor genes on chromosome 9.

¹ Oncor, Inc. provided research funding for the study described in this paper. Under an agreement between Oncor and the Johns Hopkins University, Dr. Sidransky is entitled to a share of sales royalty received by the University from Oncor. Under that agreement, the University and Dr. Sidransky also have received Oncor stock which, under University policy, cannot be traded until two years after the first commercial sales of the products related to this research. Dr. Sidransky also serves as a member of the Scientific Advisory Board of OncorMed, Inc., an Oncor subsidiary, which is commercializing some of Oncor's technology. The terms of this arrangement have been reviewed and approved by the University in accordance with its conflict of interest policies.

² To whom requests for reprints should be addressed, at Department of Otolaryngology—Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196.

Received 11/11/94. Accepted 11/30/94.

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