Genomic landscape of local prostate cancer in Sardinia population

Race and ethnicity are risk factors for prostate cancer. In the United States, African American men have the highest rate of mortality followed by Caucasians, and Asian Americans. The effects of race and ethnicity on prostate cancer are also reflected in different frequencies of ETS family fusion in different groups. ETS family fusions is the most common alteration in prostate cancer of Caucasian men at a frequency of ~50%, however, they are lower in African Americans and Chinese at 20-30%. Most of the genomic prostate cancer studies are focused on cohorts of European ancestry, leaving minority groups underrepresentation. Furthermore, in racial mixing, the ethnic contribution to risk is unclear. Sardinia population is an isolated Mediterranean population, and a purported refuge population of Neolithic ancestry with much lower incidence of prostate cancer than that in mainland Europe. Here, we conducted a genomic prostate cancer genomic study on a Sardinia cohort diagnosed with local prostate cancer. We identified a novel germline risk mutation ARSD-G320D occurring in 53 percent of the patients, somatic UGT family amplifications which occurred in 20% the patients, a novel in-frame fusion BTBD7-SLC2A5 occurred in 12 % of the patients. In addition, we pointed out that IRF8 deletion at 16q24.2 is a candidate driver in prostate cancer and patients with IRF8 deletion have worse prognosis. Our data revealed similarities and disparities in genomic alterations of prostate cancer between Sardinians and other ethnic groups. As well we have conducted a study based on Chinese prostate cancer cohort and have seen greater molecular disparities from TCGA cohort than in the Sardinian prostate cancer cohort. In Chinese cohort we have identified 37 genes significantly mutated and 20 of them have not implicated in prostate cancer in Caucasian and reveals a set of genomic markers that may inform the ethnic disparities.