Identification of a recurrent t(4;6) chromosomal translocation in prostate cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lane
Tim M
TM
Department of Medical Oncology, St. Bartholomew's Hospital, Queen Mary Wesfield School of Medicine, Queen Mary University, London, United Kingdom. MrTMLane@aol.com
Strefford
Jon C
JC
Yáñez-Muñoz
Rafael J
RJ
Purkis
Patricia
P
Forsythe
Elizabeth
E
Nia
Tiffany
T
Hines
John
J
Lu
Yong-Jie
YJ
Oliver
R Tim
RT
D045744:Cell Line, Tumor; D019457:Chromosome Breakage; D002874:Chromosome Mapping / Q000379:methods; D002894:Chromosomes, Human, Pair 4; D002896:Chromosomes, Human, Pair 6; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020079:Terminal Repeat Sequences; D014178:Translocation, Genetic / Q000235:genetics*