학술논문
Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer
Document Type
article
Author
Balabhadrapatruni VSK Chakravarthi; Pavithra Dedigama-Arachchige; Shannon Carskadon; Shanker Kalyana Sundaram; Jia Li; Kuan-Han Hank Wu; Darshan Shimoga Chandrashekar; James O Peabody; Hans Stricker; Clara Hwang; Dhananjay A Chitale; Sean R Williamson; Nilesh S Gupta; Nora M Navone; Craig Rogers; Mani Menon; Sooryanarayana Varambally; Nallasivam Palanisamy
Source
Neoplasia: An International Journal for Oncology Research, Vol 21, Iss 10, Pp 989-1002 (2019)
Subject
Language
English
ISSN
1476-5586
Abstract
We present the functional characterization of a pseudogene associated recurrent gene fusion in prostate cancer. The fusion gene KLK4-KLKP1 is formed by the fusion of the protein coding gene KLK4 with the noncoding pseudogene KLKP1. Screening of a cohort of 659 patients (380 Caucasian American; 250 African American, and 29 patients from other races) revealed that the KLK4-KLKP1 is expressed in about 32% of prostate cancer patients. Correlative analysis with other ETS gene fusions and SPINK1 revealed a concomitant expression pattern of KLK4-KLKP1 with ERG and a mutually exclusive expression pattern with SPINK1, ETV1, ETV4, and ETV5. Development of an antibody specific to KLK4-KLKP1 fusion protein confirmed the expression of the full-length KLK4-KLKP1 protein in prostate tissues. The in vitro and in vivo functional assays to study the oncogenic properties of KLK4-KLKP1 confirmed its role in cell proliferation, cell invasion, intravasation, and tumor formation. Presence of strong ERG and AR binding sites located at the fusion junction in KLK4-KLKP1 suggests that the fusion gene is regulated by ERG and AR. Correlative analysis of clinical data showed an association of KLK4-KLKP1 with lower preoperative PSA values and in young men (