Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer.
Journal
Neoplasia (New York, N.Y.)
ISSN: 1476-5586
Titre abrégé: Neoplasia
Pays: United States
ID NLM: 100886622
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
10
06
2019
revised:
22
07
2019
accepted:
23
07
2019
pubmed:
26
8
2019
medline:
22
4
2020
entrez:
26
8
2019
Statut:
ppublish
Résumé
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 (<50 years) with prostate cancer. Screening of patient urine samples showed that KLK4-KLKP1 can be detected noninvasively in urine. Taken together, we present KLK4-KLKP1 as a class of pseudogene associated fusion transcript in cancer with potential applications as a biomarker for routine screening of prostate cancer.
Identifiants
pubmed: 31446281
pii: S1476-5586(19)30273-8
doi: 10.1016/j.neo.2019.07.010
pmc: PMC6713813
pii:
doi:
Substances chimiques
KLKP1 protein, human
0
Oncogene Proteins, Fusion
0
Kallikreins
EC 3.4.21.-
kallikrein 4
EC 3.4.21.-
Tissue Kallikreins
EC 3.4.21.35
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
989-1002Subventions
Organisme : NCI NIH HHS
ID : P50 CA140388
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA176330
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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