Expression mapping at 12p12-13 in advanced prostate carcinoma.
We have previously mapped a putative prostate cancer tumor-suppressor gene to a 1-2 Mb region of 12p12-13. Initial work to identify the tumor suppressor at this locus focused on candidates previously implicated in malignancy; however, mutational and methylation analyses failed to identify significant genomic events. An alternative approach is to use expression analysis to prioritize the genes within the region of interest. This experimental design is based on the hypothesis that tumor-suppressor genes demonstrate decreased expression in tumors compared to normals. Herein, we narrow the region of interest using deletion mapping data and employ expression analysis to prioritize the genes in the minimal deleted region. Highly informative polymorphic markers spanning our region were used to assess for loss of heterozygosity in 99 tumor and normal DNA pairs. The minimal region of deletion was determined to be approximately 500 kb bounded by D12S391 and A002Q26. Publically available databases place 7 genes within this minimal deletion region. An additional 3 genes lie just outside this minimal deletion region and could possibly be inactivated by deletion of promoter, 3'-untranslated region sequences or alternative splice variants. Relative levels of expression of these 10 candidate genes were determined in 6 normal prostates, 5 local prostate tumors, 9 prostate lymph node metastases, 6 prostate cancer cell lines and 12 prostate cancer xenografts using quantitative RT-PCR. DUSP16, FLJ10298 and BCLG were significantly downregulated in both clinical tumors and cultured prostate cancer tissue, indicating that one or all may be critical to initiation or progression of prostate carcinoma.
Department of Surgery, Division of Urology, Washington University School of Medicine, 4960 Children's Place, St. Louis, MO 63110, USA. kibela@msnotes.wustl.edu
Adam S
AS
Kibel
John
J
Huagen
Chan
C
Guo
William B
WB
Isaacs
Yan
Y
Yan
Kenneth J
KJ
Pienta
Paul J
PJ
Goodfellow
D000818:Animals; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014183:Transplantation, Heterologous
D004273:DNA, Neoplasm