Genomic Instability Contributes to Aggressive Prostate Cancer

Telomeres are and caps on chromosomes, and their shortening with each cell division is thought to permit genomic instability. Researchers from the University of Texas MD Anderson Cancer Center (Texas, USA) studied a strain of mice engineered to develop prostate cancer.  The researchers observed that the lab animals all went through a process where the telomeres failed and subsequently an enzyme was activated, that allows malignant cells to become lethal, with the disease entering the spine. Two groups of mice that avoided this cycle developed only precancerous lesions or localized prostate cancer.  A comparative analysis of genetic changes in the metastatic mouse tumors and those found in metastatic human prostate cancer identified the Smad4 gene as a driver in bone metastasis. Fourteen other genes were found to be associated with human prostate cancer prognosis. Observing that: “not only did telomerase reactivation bypass the cancer progression block that arises with telomere dysfunction, it also conferred a new property – bone metastasis – that was not seen in tumors that did not go through telomere dysfunction followed by telomerase reactivation,” the study authors conclude that: “telomerase reactivation in tumor cells experiencing telomere dysfunction enables full malignant progression and provides a mechanism for acquisition of cancer-relevant genomic events endowing new tumor biological capabilities.”