Deletion of chromosomal region 6q14-16 in prostate cancer.
A detailed analysis of chromosome 6 in DNAs from prostate cancers was performed, to define a region for subsequent search for cancer genes. DNA from 4 prostate cancer cell lines and 11 xenografts was used for CGH and whole-chromosome allelotyping with polymorphic microsatellite markers. Loss of proximal 6q was studied in more detail by high-density allelotyping of xenografts, cell lines and 19 prostate tumour specimens from TURP. Seven of 15 xenografts and cell lines showed deletion of proximal 6q by CGH. Gain of 6q was found in 2 samples. Six samples showed 6p gain, and 1 had 6p loss. Allelotyping results were consistent with CGH data in 11 of 15 DNAs. In LNCaP and DU145 cells, CGH showed 6p loss and 6q loss, respectively, but 2 allelic bands were detected for many polymorphic markers on these chromosome arms. These apparent discrepancies might be explained by aneuploidy. In cell line TSU, allelotyping demonstrated chromosome 6 deletion, which was not clearly detected by CGH, indicating loss of 1 copy of chromosome 6 followed by gain of the retained copy during progressive tumour growth. Loss of heterozygosity was detected in 9 of 19 TURP specimens. Combining all data, we found a common minimal region of loss at 6q14-16 with a length of 8.6 Mbp flanked by markers D6S1609 and D6S417. One hundred and twenty-three STSs, ESTs, genes and candidate genes mapping in this interval were used to screen xenografts and cell lines for HDs, but none was detected. In summary, chromosome region 6q14-16 was deleted in approximately 50% of the prostate cancer specimens analysed. The high percentage of loss underscores the importance of genes within this region in prostate cancer growth.
Verhagen
Paul C M S
PC
Department of Urology, University Hospital Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. verhagen@urol.azr.nl
Hermans
Karin G L
KG
Brok
Mariel O
MO
van Weerden
Wytzke M
WM
Tilanus
Marcel G J
MG
de Weger
Roel A
RA
Boon
Tom A
TA
Trapman
Jan
J
D000483:Alleles; D000818:Animals; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009693:Nucleic Acid Hybridization; D011471:Prostatic Neoplasms / Q000235:genetics*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured