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Major Study Links Gene to Drug Resistance in Testicular Cancer

XRCC2 mutation may explain resistance to platinum-based therapy

A major research study has uncovered several new genetic mutations that could drive testicular cancer –– and also identified a gene that may contribute to tumors becoming resistant to current treatments.

The study is the first to use state-of-the-art sequencing technology to explore testicular germ-cell tumors, which make up the majority of testicular cancers and are the most common cancers in young men.

The study was led by scientists at the Institute of Cancer Research in London, and was published in Nature Communications.

The investigators used a genetic technique called whole-exome sequencing to examine tumor samples from 42 patients with testicular cancer. They uncovered a number of new chromosome duplications and other abnormalities that could contribute to the development of this cancer, as well as confirming a previous association with the gene KIT.

Their study also found defective copies of a DNA repair gene called XRCC2 in a patient who had become resistant to platinum-based chemotherapy. They were able to verify the link between XRCC2 and platinum resistance by sequencing an additional sample from another platinum-resistant tumor.

Although testicular cancer generally responds well to treatment, resistance to platinum-based chemotherapy is associated with a poor long-term survival rate, according to the authors. The new research provides a clue to why approximately 3% of patients develop resistance to platinum-based chemotherapy, as well as new insights into testicular germ-cell tumors.

Team leader Dr. Clare Turnbull said: “Our study is the largest comprehensive sequencing study of testicular tumors published to date, describing their mutational profile in greater detail than has been possible using previous technologies. We have identified new potential driver mutations for this type of cancer, and provided new evidence of a link between mutations in the gene XRCC2 and platinum treatment-resistant tumors.

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

Source: ICR; January 22, 2015.


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