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

PURPOSE: 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. MATERIALS AND 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.

Predicting and preventing post-herpetic neuralgia: are current risk factors useful in clinical practice?

Post-herpetic neuralgia (PHN) following acute herpes zoster remains a significant cause of neuropathic pain especially in the elderly. Early treatment of the zoster rash with antiviral agents, such as aciclovir remains one of the few measures proven to reduce the incidence and duration of PHN albeit only in a subset of patients. It is therefore crucial that the physician who first sees a case of zoster identifies those patients who are most likely to develop long-term pain and treats them accordingly. In particular, prodrugs such as famciclovir and valaciclvoir may be more beneficial in reducing PHN than the shorter acting aciclovir, but can be more expensive. Measures that could be used to predict patients likely to develop PHN would also facilitate the evaluation of early use of antiepileptic, anti-inflammatory and analgesic agents in the prevention of PHN. In a prospective study of 280 herpes zoster (HZ) cases seen by the general practitioner (GP) we evaluated the predictive value of five clinical factors identified in clinical trials as associated with a higher likelihood of PHN. A visual analogue score (VAS) over 5 and/or age over 50 correctly identified all subjects with PHN at 3 and 6 months, respectively. However, the specificity of this prediction was low because as many as 81% and 85% of those aged over 50 recovered within 3 and 6 months, respectively. Better methods are needed to identify patients over 50 at most risk of PHN that enable GPs to better allocate their resources with respect to HZ treatment.