Lane Tim M, Strefford Jon C, Yáñez-Muñoz Rafael J, Purkis Patricia, Forsythe Elizabeth, Nia Tiffany, Hines John, Lu Yong-Jie, Oliver R Tim
Department of Medical Oncology, St. Bartholomew's Hospital, Queen Mary Wesfield School of Medicine, Queen Mary University, London, United Kingdom.
J Urol. 2007 May;177(5):1907-12. doi: 10.1016/j.juro.2007.01.001.
We developed and describe a practical method by which primary prostate cancer specimens can be screened for recurrent chromosomal translocations, which is a potential source of fusion genes, as well as a process by which identified translocations can be mapped to define the genes involved.
A series of 7 prostate cancer cell lines and 25 transiently established primary cell cultures, which were sourced from tissue harvested at 16 radical prostatectomies and 9 channel transurethral prostate resections, were screened for chromosomal translocations using multiplex-fluorescence in situ hybridization technology. A series of fluorescence in situ hybridization based breakpoint mapping experiments were performed to identify candidate genes involved in regions associated with recurrent translocation.
Our analysis identified the repetition of 2 translocations in prostate cancer lines, that is t(1;15) and t(4;6), at a frequency of 28% and 57%, respectively. More significantly 4 of the 25 subsequently established primary cultures (16%) also revealed a t(4;6) translocation. Using the LNCaP cell line the breakpoints involved were mapped to the t(4;6)(q22;q15) region and a number of candidate genes were identified.
We found that the t(4;6) translocation is also a repeat event in primary cell cultures from malignant prostate cancer. Breakpoint mapping showed that the gene UNC5C loses its promoter and first exon as a direct result of the translocation in the 4q22 region. As such, we identified it as a possible contributor to a putative fusion gene in prostate cancer.
