Association Of The Prostate Cancer Risk Mutation G84e In Hoxb13 With The Subtype Of Ets Fusion Negative Adenocarcinoma With Early Age Of Diagnosis.

5021 Background: HOXB13 was discovered as the first prostate cancer (PrCa) specific high-risk susceptibility gene. The most prevalent HOXB13 germline mutation in PrCa patients of European descent is HOXB13G84E, which likely originated in Northern Europe. Previous molecular examination of a set of G84E driven tumors suggested a distinct somatic phenotype, where oncogenic ETS gene fusions appear at unusually low frequencies as compared to the general prevalence of ETS fusions in PrCa (22 % vs approx. 50 %). Methods: We have analyzed 942 cases from three European ancestry populations for the coincidence of HOXB13 G84E and the most common ETS fusion, TMPRSS2-ERG(T2E), in corresponding tumor samples. Results: While the prevalence of T2E fusions was similar among study sites (range: 56.5% - 60.7%), the frequency of G84E genotypes differed markedly between US (1.5%), German (3.6%) and Finnish samples (8.3%). Despite the expected frequency gradient among study populations, all subsamples showed a strong enrichmen...