3 DISTINCT COMMONLY DELETED REGIONS OF CHROMOSOME ARM 16Q IN HUMAN PRIMARY AND METASTATIC PROSTATE CANCERS

Human prostate cancers frequently show loss of heterozygosity (LOH) at loci on the long arm of chromosome 16 (16q). In this study, we analyz ed prostate cancer specimens from 48 patients (Stage B, 20 cases; Stag e C, 10 cases; cancer death, 18 cases) for allelic loss on 16q, using either restriction fragment length polymorphism (RFLP)- or polymerase chain reaction (PCR)-based methods. Allelic losses were observed in 20 (42%) of 48 cases, all of which were informative with at least one lo cus. Detailed deletion mapping identified three distinct commonly dele ted regions on this chromosome arm: q22.1-q22.3, q23.2-q24.1, and q24. 3-qter. On the basis of a published sex-averaged framework map, the es timated sizes of the commonly deleted regions were 4.7 (16q22.1-q22.3) , 17.2 (16q23.2-q24.1) and 8.4 cM (16q24.3-qter). Allelic losses on 16 q were observed more frequently in the cancer-death cases (11 of 18; 6 1%) than in early-stage tumor cases (9 of 30; 30%; P < 0.05). In 7 of 11 patients from whom DNA was available from metastatic cancers as wel l as from normal tissues and primary tumors, the primary cancer foci h ad no detectable abnormality of 16q, but the metastatic tumors showed LOH. These results suggest that inactivation of tumor suppressor genes on 16q plays an important role in the progression of prostate cancer. We also analyzed exons 5-8 of the E-cadherin gene, located at 16q22.1 , in tumor DNA by means of PCR-single strand conformation polymorphism and direct sequencing, but we detected no somatic mutations in this c andidate gene. (C) 1996 Wiley-Liss, Inc.