Human prostate cancers frequently show loss of heterozygosity (LOH) at loci on the long arm of chromosome 16 (16q). In this study, we analyzed prostate cancer specimens from 48 patients (Stage B, 20 cases; Stage 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 locus. Detailed deletion mapping identified three distinct commonly deleted 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 estimated 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 16q were observed more frequently in the cancer‐death cases (11 of 18; 61%) 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 well as from normal tissues and primary tumors, the primary cancer foci had 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 candidate gene. Genes Chromosom Cancer 17:225–233 (1996). © 1996 Wiley‐Liss, Inc.

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To examine the role of human chromosome 10 in development of prostatic cancer, we introduced human chromosome 10 into highly metastatic rat prostatic cancer cells by microcell-mediated chromosome transfer. Microcell hybrid cells introduced with human chromosome 10 showed suppression of the metastatic ability to the lung to some extent without any suppression of tumorigenicity, although the tumor growth rate decreased slightly. To minimize the region that contains metastasis suppressive activity, the hybrid cells in metastasis foci of lung were established in culture and reanalyzed for portions of human chromosome 10 retained in the metastasis tissues. Cytogenetic and molecular analyses demonstrated that loss of the region between 10cen and D10S215 on human chromosome arm 10q was related to expression of the metastatic phenotype. These results demonstrate that the region between 10cen and D10S215 on human chromosome arm 10q contains at least one of the metastasis suppressor genes for rat prostatic cancer.

Our previous studies demonstrated that human chromosome 8 contains metastasis suppressor gene(s) for rat prostate cancer. However, it is still unknown which portion of human chromosome 8 is associated with suppression of metastatic ability, because all of the clones in which metastatic ability is suppressed contain at least one copy of intact human chromosome 8. In the present study, we used the irradiated microcell‐mediated chromosome transfer technique to enrich for specific chromosomal arm deletions of selected chromosomes. The resultant series of human chromosomes 8 with a variety of chromosomal deletions was introduced into highly metastatic Dunning rat prostate cancer cells. All of the resultant microcell hybrids showed reduced metastatic ability. To obtain a smaller size of human chromosome 8 and to locate further the region of metastasis suppressor gene(s), the most reduced size of human chromosome 8 that was generated with the initial irradiated chromosome transfer was retransferred into the Dunning cancer cells without irradiation. The resultant microcell hybrids were analyzed to determine which portion of human chromosome 8 suppressed the metastatic ability of the recipient cells. This analysis demonstrates that the portion of human chromosome 8 containing metastasis suppressor gene(s) for rat prostate cancer cells lies on human chromosome segment 8p21‐p12, where frequent allelic losses have been detected in allelotype analyses of human prostate cancer. This suggests that one of the metastasis suppressor genes for rat prostate cancer on human chromosome 8 may also play an important role in the progression of human prostate cancer. Genes Chromosom Cancer 17:260–268 (1996). © 1996 Wiley‐Liss, Inc.

Human prostate cancers frequently show loss of heterozygosity (LOH) at loci on the long arm of chromosome 16 (16q). In this study, we analyzed prostate cancer specimens from 48 patients (Stage B, 20 cases; Stage 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 locus. Detailed deletion mapping identified three distinct commonly deleted 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 estimated 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 16q were observed more frequently in the cancer-death cases (11 of 18; 61%) 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 well as from normal tissues and primary tumors, the primary cancer foci had 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 candidate gene.