Distinct deleted regions on chromosome segment 16q23-24 associated with metastases in prostate cancer.
Cadherins (CDH) are cell adhesion molecules and their dysfunctions have been implicated in the development of cancer metastases. Several cadherin genes are tandemly located on 16q, which is frequently deleted in prostate cancer. We therefore used 22 markers on 16q to localize important deleted regions in metastases of this tumor. We found 16q deletions in 24/32 (75%) tumors. 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 (D16S515-D16S516) and CDR4 (D16S520-D13S3028), were strongly associated with metastases and increased Gleason score. Reduced CDH1 (E-cadherin) expression was seen in 16/32 (50%) tumors, but the CDH1 gene is not within either of these two regions. Sequencing analysis for all 16 exons of the CDH1 gene did not reveal any mutations in 10 tumors, including three brain metastases with both 16q22.1 deletion and absent E-cadherin expression. Our results implicate other, yet unidentified genes on 16q23-24 to be the frequent targets of mutations and deletions in prostate cancer metastases.
Li
C
C
Department of Urology, Karolinska Hospital, Stockholm, Sweden. Chunde.Li@kirurgi.ki.se
Berx
G
G
Larsson
C
C
Auer
G
G
Aspenblad
U
U
Pan
Y
Y
Sundelin
B
B
Ekman
P
P
Nordenskjöld
M
M
van Roy
F
F
Bergerheim
U S
US
D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
D015820:Cadherins