| THE
ROLE OF CHROMOSOME TRANSLOCATION IN THE PROGRESSION OF
PROSTATE CANCER.
Dr Yong-Jie Lu St Bartholomew's Hospital and the London School of Medicine |
 |
The aim of this project is to investigate the potential of using recurrent chromosome translocations to predict the clinical outcome of prostate cancer patients. Chromosomes are the entities within cells in which carry genetic material. Chromosome translocation is a genetic event which two chromosomes swap parts to form abnormal chromosomes. This can lead to the fusion of two genes where the chromosome rejoin. Chromosome translocations and fusion genes can result in cancer development. In many cases, patients bearing tumours with certain chromosome translocations die of the cancer sooner than people who do not. Although it is now known that chromosome translocations play an important role in the development of tumours in the blood, their role in prostate cancer is not well studied. Recently fusion of a prostate specific gene, TMPRSS2, with a number of other genes including ERG and ETV1 has been found in a high frequency of prostate cancers. In our laboratory, we have also found a recurrent chromosome translocation which involves transfer of genetic material between chromosomes 4 and 6, namely t(4;6). In this project we have studied the frequency and clinical significance of these chromosome translocations/fusion genes in a large series of prostate cancer samples.
We analysed 417 cases of prostate cancer using a colour-coded method in order to identify the t(4;6) chromosome translocation.. In this method, each chromosome was painted in a different colour and 24 normal tissue samples were used as controls. The t(4;6) was found at a high frequency in the prostate cancer samples while it is absent from the normal controls. This finding is currently being followed-up in a separate project to determine whether the t(4;6) can be used to predict patient’s clinical outcome, particularly in patients where the cancer was diagnosed at a early stage.
Using the same technology, we have also checked the frequency of the chromosome translocation responsible for the TMPRSS2/ETV1 gene fusion in 42 prostate cancer samples. It was however only detected in 2 cases. Using a different method to detect the activity of the fusion gene in 27 prostate cancer samples, we did not find any abnormal cases. Our data correlated with the results from studies performed by other researchers that either detected TMPRSS2:ETV1 fusion at a very low frequency or did not detect it at all. Therefore, we focused our study on the t(4;6) and TMPRSS2:ERG fusion instead of further pursuing the TMPRSS2/ETV1 gene fusion study.
In parallel with the colour coded analysis for chromosome translocations, we also analysed the TMPRSS2:ERG fusion gene status in our prostate cancer samples by detecting the product of the fusion gene. We found the product of the TMPRSS2:ERG fusion gene in 44% (12 out of 27) of prostate cancer samples. More importantly, we detected the TMPRSS2:ERG fusion gene in tumour cells circulating in blood in 6 out of 10 individuals. This indicates the potential to monitor prostate cancer metastasis by a blood test to detect the fusion gene.
Research summary final report dated 11 November 2007
Project 2005/10