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Coding Region of NKX3.1, a Prostate-Specific Homeobox Gene on 8p21, Is Not Mutated in Human Prostate Cancers¹

Division of Hematology/Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007-2197 [H. J. V., E. P. G.]; Department of Molecular Biology, Human Genome Sciences Inc., Rockville, Maryland 20850 [M. A., V. M., K. C. C.]; and Brady Urological Institute, Johns Hopkins University, Baltimore, Maryland 21287 [G. S. B.]

Loss of heterozygosity at chromosome 8p21–22 is common in human prostate cancer, suggesting the presence of one or more tumor suppressor genes at this locus. A homeobox gene that is expressed specifically in adult human prostate, NKX3.1, the expression of which is regulated by androgen, maps to chromosome 8p21. Fine structure in situ mapping showed that NKX3.1 is proximal to MSR32 (macrophage scavenge scavenger receptor type II) and LPL (human lipoprotein lipase) and very close to NEFL (human neurofilament light chain) on 8p21. Single-strand conformational polynorphism analysis of 48 radical prostatectomy cancer specimens and 3 metastases for the entire coding region of NKX3.1 showed no tumorspecific sequence alterations in 50 specimens and total absence of the gene in 1 specimen known to have a biallelic deletion of 8p21. NKX3.1 was found to have a polymorphism at nucleotide 154 in codon 52 that resulted in a CGCTGC sequence change and an ArgCys amino acid alteration (R52C). This polymorphism was present in 20% of DNA smaples. If NKX3.1 is a target of the 8p21 LOH, it is not via disruption of the coding region of the gene.

¹ This work was supported by NIH Grant CA57178 to E.P.G. and by an award from the CaPCURE Foundation.

² These authors contributed equally to this work.

³ To whom requests for reprints should be addressed, at Division of Hematology/Oncology, Lombardi Cancer Center, Georgetown University Medical Centcer, 3800 Reservoir Road NW, Washsington, DC 20007-2197. Phone: (202) 687-2207; Fax: (202) 784-1229; E-mail: gelmanne@gunet.georgetown.edu.

Received 6/26/97. Accepted 8/28/97.

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