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Loss of Heterozygosity at Chromosome 16 q in Prostate Adenocarcinoma : Identification of Three Independent Regions 1

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, CDHJ at 16q22.1, is dysregulated in prostate cancer. However, no specific deletionmap has been constructedfrom prostatetumorsto determine whether CDHJ 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 CDHJ. We examined the pattern of allelic imbal ance in prostate tissue from 22 patients with confined prostate tumors, 22 with local extracapsular extension, and 15 with metastatic forms, using 14 CA microsateffite repeats on 16q. Thirty-five of the 59 tumors tested showed LOH for at least one marker. We found evidence of 16q mono somy 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 patho genesisof prostatecancer.Thefirstregionis telomericandliesat 16q24.3 between markers D16S520 and D16S413; the second, the most centro meric region in the 16q22.1 band, and limited by markers D16S347 and D16S318, is close to the CDHJ gene; the third, intermediate region, at 16q23.2, is bracketed by loci D16S518 and D16S507 The rate ofLOH 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.