Distinct deleted regions on chromosome segment 16q23-24 associated with metastases in prostate cancer

Cadherins (CDH) are cell adhesion molecules and their dysfunctions have bee n implicated in the development of cancer metastases. Several cadherin gene s are tandemly located on 16q, which is frequently deleted in prostate canc er. We therefore used 22 markers on 16q to localize important deleted regio ns in metastases of this tumor. We found 16q deletions in 24/32 (75%) tumor s. All lymph node and brain metastases showed extensive deletions, while 52 % of primary tumors displayed limited deletions. Commonly deleted regions ( CDRs) on 16q23-24, CDR2 (D161515-D16S516) and CDR4 (D16S520-D13S3028), were strongly associated with metastases and increased Gleason score. Reduced C DH1 (E-cadherin) expression was seen in 16/32 (SOX) tumors, but the CDH1 ge ne is not within either of these two regions. Sequencing analysis for all 1 6 exons of the CDH1 gene did not reveal any mutations in 10 tumors, includi ng three brain metastases with both 16q22. 1 deletion and absent E-cadherin expression. Our results implicate other, yet unidentified genes on 16q23-2 4 to be the frequent targets of mutations and deletions in prostate cancer metastases. Genes Chromosomes Cancer 24: 175-182, 1999. (C) 1999 Wiley-Liss , Inc.