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Loss of Heterozygosity at Chromosome 16q in Prostate Adenocarcinoma: Identification of Three Independent Regions¹

Laboratoire d'Oncogénétique, Centre René Huguenin, 9 rue Gaston Latouche, F-92211 St-Cloud, France [A.L., K.D., R.L.]; Department d'Urologie, Centre Hospitalier Universitaire Saint-Louis, F-75010 Paris, France [O. C.]; and Departement d'Urologie, Hôpital de la Cavale Blanche, F-29609 Brest, France [G. F.]

Loss of heterozygosity (LOH) on chromosome arm 16q is one of the most consistent genetic alterations in sporadic prostate cancer and may be involved in cancer development through inactivation of tumor suppressor genes. A candidate tumor suppressor gene on this chromosome arm, CDH1 at 16q22.1, is dysregulated in prostate cancer. However, no specific deletion map has been constructed from prostate tumors to determine whether CDH1 is the potential target gene for the observed LOH on 16q. To narrow down the region of 16q loss, we constructed a detailed deletion map that incorporates CDH1. We examined the pattern of allelic imbalance in prostate tissue from 22 patients with confined prostate tumors, 22 with local extracapsular extension, and 15 with metastatic forms, using 14 CA microsatellite repeats on 16q. Thirty-five of the 59 tumors tested showed LOH for at least one marker. We found evidence of 16q monosomy in 5 cases and partial allelic loss in 30. Our data provide evidence that three different target regions on 16q might be involved in the pathogenesis of prostate cancer. The first region is telomeric and lies at 16q24.3 between markers D16S520 and D16S413; the second, the most centromeric region in the 16q22.1 band, and limited by markers D16S347 and D16S318, is close to the CDH1 gene; the third, intermediate region, at 16q23.2, is bracketed by loci D16S518 and D16S507.

The rate of LOH at 16q24.3 was significantly higher in metastatic forms (80%; 12 of 15) than localized forms (32%; 7 of 22), pointing to a gene related to invasiveness in prostate cancer.

¹ This work was supported by the Ligue Nationale de Lutte Contre le Cancer, the Comités Régionaux des Hauts de Seine, du Val d'Oise et des Yvelines, and the Association pour la Recherche sur les Tumeurs Prostatiques.

² To whom requests for reprints should be addressed. R. L. is a research director with the Institut National de la Santé et de la Recherche Médicale.

Received 12/ 2/96. Accepted 1/27/97.

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