Abstract C75: Unique SPOP somatic mutations in African American prostate cancer

Abstract

Abstract SPOP (Speckle-type POZ protein) is a tumor suppressor in prostate cancer (PCa). Somatic heterozygous missense mutations in SPOP have been reported in up to 15% of PCa in Caucasian American (CA). However, the mutation frequency and the genetic role of SPOP in African American (AA) PCa are currently unknown. We sequenced exons 6 and 7 of the SPOP gene for somatic mutations in 49 AA prostate tumor tissues collected in the Southern Louisiana area and identified five (10%) tumors carrying heterozygous missense mutations and one tumor carrying a novel synonymous variant. Intriguingly, all mutations are clustered in exon 6 and change conserved amino acids. Moreover, three mutations represent novel mutations and unique to AA PCa. To further identify unique SPOP somatic mutations in AA PCa, we expanded mutation screening to all of the other exons of the SPOP gene but no additional coding variant or deletion/insertion was identified. Quantitative RT-PCR analysis indicates that the SPOP mutations in AA prostate tumors reduced SPOP RNA levels in tumors compared with SPOP levels in their adjacent normal prostate tissues; therefore, supporting the notion of SPOP as a tumor suppressor gene. These results indicate that AA prostate tumors carry similar frequency but a unique profile of SPOP somatic mutations as in Caucasian PCa. The clinical relevance and the pathological significance of SPOP mutations in AA PCa will be discussed. Citation Format: Eric L. Buckles, Chiping Qian, Sumana Majumdar, Jovanny Zabaleta, Wanguo Liu. Unique SPOP somatic mutations in African American prostate cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C75. doi:10.1158/1538-7755.DISP13-C75