Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1.
RESULTS
By differential display we isolated a new cDNA-fragment, named C13, that is downregulated in malignant prostate tissues. Northern hybridization revealed the fragment to be part of 3.0 and 4.4 kb mRNAs. Fluorescence in situ hybridization, Southern blotting and radiation hybrid mapping demonstrated a chromosomal localization of C13 on 13q12-14 closest to the SHGC-34125 marker. In the 5% chromosomal environment of C13 we detected changes of the allelic status in 13 of 21 prostate cancers. A downregulation was detected at the mRNA level in patients with advanced carcinoma. The 3.0 kb full length cDNA clone encodes a protein with an open reading frame of 2,202 bp or 733 amino acids. The corresponding protein contains a putative nuclear localization signal, several glutamine clusters and an alpha-helix-rich domain. By in situ RNA hybridization we could demonstrate the mainly epithelial expression of the C13 mRNA in prostatic tissue.


CONCLUSIONS
The localization of C13 between the tumor suppressor genes BRCA-2 and RB-1, the detected allelic imbalances, the downregulation of its mRNA in some prostatic cancer tissues, the epithelial expression and the described protein structure suggest that this gene encodes a protein that may have tumor or metastasis suppressing function in prostate tissue.
Schmidt
U
U
Department of Urology, Technical University of Dresden, Dresden, Germany.
Fiedler
U
U
Pilarsky
C P
CP
Ehlers
W
W
Füssel
S
S
Haase
M
M
Faller
G
G
Sauter
G
G
Wirth
M P
MP
D024682:BRCA2 Protein; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D021101:Radiation Hybrid Mapping; D019105:Random Amplified Polymorphic DNA Technique; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D024682:BRCA2 Protein; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016160:Retinoblastoma Protein; D014157:Transcription Factors