Genetic Root Identified For Early-Onset Prostate Cancer

Early-onset prostate cancer (EOPC) requires early diagnosis and definitive treatment due to the long life expectancy of younger patients and their higher risk of dying from the disease.

Deep sequencing-based genomics analysis has been used to compare the genomic alteration landscapes of EOPC patients with those with the classical elderly-onset prostate cancer.

Scientists at the European Molecular Biology Laboratory (EMBL; Heidelberg, Germany) sequenced the entire genetic code of cells in 11 tumors from EOPC patients, comparing it with the code in tumors from seven patients with elderly-onset prostate cancer. They used these genomics data, together with a large-scale tissue microarray (TMA)-based validation platform, to pinpoint molecular features linked with early disease occurrence.

The investigators found that the receptor that binds testosterone, called the androgen receptor, is very active in tumors from young patients, causing a number of genes to rearrange and become cancer promoting. The genomes of elderly prostate cancer patients primarily showed abnormalities that were not caused by the androgen receptor's activity. Data from more than 10,000 additional patients showed that androgen receptor activity and corresponding gene rearrangements were indeed higher in younger patients.

Jan Korbel, PhD, the cosenior author of the study, said, "It's been unclear whether prostate cancer in the young is explainable by a different mechanism than prostate cancer in the elderly. Our study implicates a different cause of disease in young patients. Interestingly, young men have generally higher testosterone levels than elderly men, which raises the question of whether high physiological levels of testosterone in young men may be linked with early-onset prostate cancer, a question that we are keen to address in the future." The authors concluded that their findings demonstrate striking age-dependent differences in the mechanistic landscapes of structural genomic alterations in a common cancer. The study was published on February 11, 2013, in the journal Cancer Cell.

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