TP53, SPOP and PIK3CA Genes Status in Prostate Cancer

Abstract

Recent advances in molecular biology make the identification of prostate cancer (PC) subsets a priority for more understanding of the molecular pathogenesis and treatment options. Genetic alterations in many genes such as TP53, SPOP and PIK3CA genes have been reported in PC with variable frequencies worldwide. We aimed to investigate genetic alterations in the hotspot lesions of TP53, SPOP and PIK3CA genes by direct sequencing and the expression of TP53 and PIK3CA by RT-PCR in prostate cancer, and to explore the correlation between TP53, SPOP and PIK3CA alterations and tumorigenesis of prostate cancer. Seventy-nine FFPE prostate samples from patients who underwent radical prostatectomy were obtained, subjected to genomic DNA extraction and sequenced for mutations in exons 5, 6, 7 and 8 of TP53 gene, exons 4 and 5 of SPOP gene and exons 9 and 20 of PIK3CA gene. RT-PCR was performed for the expression evaluation of the PIK3CA gene. Our results showed a high frequency of TP53 mutations (11/79, 13.9 %) in the selected population. On the other hand, SPOP and PIK3CA genes did not show any genetic alteration in the sequenced exons. PIK3CA gene overexpression was detected in 6% of the cohort by RT-PCR. TP53 mutation is the most frequent genetic alteration and likely has a major role in the pathogenesis of PC in the Jordanian population.<br />.

Keywords: PIK3CA; Prostate Cancer; SPOP; Tp53; p53.

Figure 1

A Representative Chromatogram of the Detected Mutations in the TP53 Gene. A: Homologous mutation GCC/ACC (A1358T) (exon 5), B: CTG/CCG (L145P) (exon 5), C: TGC/TAC (C176Y) (exon 5), D: Rs868157297 (G/GA) (intron 4), E: Homologous mutation CGA/TGA (R196*) (exon 6), F: CTT/CGT (L194R) (exon 6), G: CGA/CGG (R213R) (exon 6) H: TAC/AAC (Y234N) (exon 7), I: CGT/TGT (R273C) (exon 8)