Universität zu Köln

Menon, Roopika, Deng, Mario, Rueenauver, Kerstin, Queisser, Angela, Pfeifer, Martin, Offermann, Anne, Boehm, Diana, Vogel, Wenzel, Scheble, Veit, Fend, Falko, Kristiansen, Glen, Wernert, Nicolas, Oberbeckmann, Nicole, Biskup, Saskia, Rubin, Mark A., Shaikhibrahim, Zaki and Perner, Sven (2013). Somatic copy number alterations by whole-exome sequencing implicates YWHAZ and PTK2 in castration-resistant prostate cancer. J. Pathol., 231 (4). S. 505 - 517. HOBOKEN: WILEY. ISSN 1096-9896

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Abstract

Castration-resistant prostate cancer (CRPC) is the most aggressive form of prostate cancer (PCa) and remains a significant therapeutic challenge. The key to the development of novel therapeutic targets for CRPC is to decipher the molecular alterations underlying this lethal disease. The aim of our study was to identify therapeutic targets for CRPC by assessing somatic copy number alterations (SCNAs) by whole-exome sequencing on five CRPC/normal paired formalin-fixed paraffin-embedded (FFPE) samples, using the SOLiD4 next-generation sequencing (NGS) platform. Data were validated using fluorescence in situ hybridization (FISH) on a PCa progression cohort. PTK2 and YWHAZ amplification, mRNA and protein expression were determined in selected PCa cell lines. Effects of PTK2 inhibition using TAE226 inhibitor and YWHAZ knock-down on cell proliferation and migration were tested in PC3 cells in vitro. In a larger validation cohort, the amplification frequency of YWHAZ was 3% in localized PCa and 48% in CRPC, whereas PTK2 was amplified in 1% of localized PCa and 35% in CRPC. YWHAZ knock-down and PTK2 inhibition significantly affected cell proliferation and migration in the PC3 cells. Our findings suggest that inhibition of YWHAZ and PTK2 could delay the progression of the disease in CRPC patients harbouring amplification of the latter genes. Furthermore, our validated whole-exome sequencing data show that FFPE tissue could be a promising alternative for SCNA screening using next-generation sequencing technologies. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Menon, Roopika UNSPECIFIED UNSPECIFIED UNSPECIFIED Deng, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueenauver, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Queisser, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfeifer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Offermann, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehm, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogel, Wenzel UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheble, Veit UNSPECIFIED UNSPECIFIED UNSPECIFIED Fend, Falko UNSPECIFIED UNSPECIFIED UNSPECIFIED Kristiansen, Glen UNSPECIFIED UNSPECIFIED UNSPECIFIED Wernert, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED Oberbeckmann, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Biskup, Saskia UNSPECIFIED UNSPECIFIED UNSPECIFIED Rubin, Mark A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shaikhibrahim, Zaki UNSPECIFIED UNSPECIFIED UNSPECIFIED Perner, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-471259
DOI:	10.1002/path.4274
Journal or Publication Title:	J. Pathol.
Volume:	231
Number:	4
Page Range:	S. 505 - 517
Date:	2013
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1096-9896
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOCAL ADHESION KINASE; ERG REARRANGEMENT; C-MYC; GENE; TMPRSS2-ERG; 14-3-3-ZETA; ABIRATERONE; EXPRESSION; CARCINOMA; GENOME Multiple languages Oncology; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47125