Scientists at The Institute of Cancer Research, London, have uncovered several new genetic mutations that drive testicular cancer, and also identified a gene which may contribute to tumours becoming resistant to existing treatment. The finding, based on the whole-exome sequencing technology, published in the journal Nature Communications.

The research is the first to use state-of-the-art sequencing technology to look into the detail testicular germ cell tumours from 42 patients at the Royal Marsden NHS Foundation Trust, which make up the vast majority of testicular cancers and are the most common cancers in young men.

In the research, they uncovered a number of new chromosome duplications and other abnormalities that could result in the development of this cancer. For instance, they found defective copies of a DNA repair gene called XRCC2 in a patient who had become resistant to platinum-based chemotherapy, as well as verifying the link between XRCC2 and platinum resistance by sequencing an additional sample from another platinum-resistant tumour.

Although generally testicular cancer responds well to treatment, resistance to platinum-based chemotherapy is linked to a poor long-term survival rate. The research provides a clue to why around 3 percent of patients develop resistance to platinum chemotherapy, as well as new insights into testicular germ cell tumours generally.

A researcher, involved in this study, said ” we have identified new potential driver mutations for this type of cancer in the largest comprehensive sequencing study of testicular tumours published to date, and provided new evidence of a link between mutations in the gene XRCC2 and platinum treatment-resistant tumours. ”

He added, “we now need additional studies with a larger number of patients, focusing in particular on platinum-resistant tumours, to help our discoveries lead to new options for those unlucky men whose cancer progresses in spite of the best available treatments.

Another researcher said, ” survival rates for testicular cancer are generally very good, but a subset of men don’t respond to standard platinum chemotherapy, and the new research has identified a possible genetic cause for that drug resistance. Knowing which are the key genes driving a cancer’s development or helping it dodge the effects of chemotherapy is crucial to help us use current drugs more effectively and to design the next generation of drugs for personalized medicine.”