Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1

• Published in: The Prostate 2001-05, Vol.47 (2), p.91-101
• Main Authors: Schmidt, U., Fiedler, U., Pilarsky, C.P., Ehlers, W., Füssel, S., Haase, M., Faller, G., Sauter, G., Wirth, M.P.
• Format: Article
• Language: English
• Subjects: BRCA-2; BRCA2 Protein; chromosome 13; Chromosomes, Human, Pair 13 - genetics; differential display; DNA, Complementary - genetics; DNA, Complementary - isolation & purification; DNA, Complementary - metabolism; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; DNA, Neoplasm - metabolism; Gene Expression Profiling; Genes, Tumor Suppressor; Humans; In Situ Hybridization, Fluorescence; Loss of Heterozygosity; Male; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; prostate carcinoma; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - genetics; Radiation Hybrid Mapping; Random Amplified Polymorphic DNA Technique; RB-1; Retinoblastoma Protein - chemistry; Retinoblastoma Protein - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; Transcription Factors - chemistry; Transcription Factors - genetics
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.1051

METHODS AND 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 α‐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 supressor 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. Prostate 47:91–101, 2001. © 2001 Wiley‐Liss, Inc.