Researchers have described a new class of pseudogene-associated fusion transcript in prostate cancer that has potential application as a therapeutic target and biomarker for early prostate cancer detection.
The fusion transcript KLK4-KLKP1 is a urine biomarker that is formed when the protein coding gene KLK4 fuses with the noncoding pseudogene KLKP1.
The research, which was published in Neoplasia (2019; 21:989-1002), was carried out at the Henry Ford Health System. The authors screened 659 radical prostatectomy samples and found the expression of KLK4-KLKP1 fusion gene in 32% of patients. Interestingly, they discovered that KLK4-KLKP1 expression was notably higher in younger prostate cancer patients under 50 years of age.
They also confirmed KLK4-KLKP1’s role in cell proliferation, cell invasion, intravasation, and tumor formation using in vitro and in vivo functional assays.
“The significant and novel aspect of this gene fusion is the conversion of the non-coding KLKP1 pseudogene into a protein coding unit after the fusion. KLKP1 pseudogene without fusion is expressed only in normal prostate tissue, but the fusion gene is expressed only in prostate cancer,” said study author Nallasivam Palanisamy, MSc, MPhil, PhD, of Henry Ford Health System, Detroit and the University of Michigan Medical School, Ann Arbor.
The study also points to a long-held misconception about the role of pseudogenes in diseases like cancer.
“It is for the first time we show the prostate cancer-specific expression of a pseudogene, KLKP1. Pseudogenes were once thought to be junk DNA without any known functions. However, we were able to show the importance of pseudogenes in cancer using the new technologies and approaches available in the next generation sequencing and precision medicine era.” he said.