Molecular Composition of Genomic TMPRSS2-ERG Rearrangements in Prostate Cancer

Krumbholz M, Agaimy A, Stöhr R, Burger M, Wach S, Taubert H, Wullich B, Hartmann A, Metzler M (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Disease Markers IOS Press

Book Volume: 2019

DOI: 10.1155/2019/5085373

Abstract

There is increasing interest in the use of cell-free circulating tumor DNA (ctDNA) as a serum marker for therapy assessment in prostate cancer patients. Prostate cancer is characterized by relatively low numbers of mutations, and, in contrast to many other common epithelial cancers, commercially available single nucleotide mutation assays for quantification of ctDNA are insufficient for therapy assessment in this disease. However, prostate cancer shares some similarity with translocation-affected mesenchymal tumors (e.g., leukemia and Ewing sarcoma), which are common in pediatric oncology, where chromosomal translocations are used as biomarkers for quantification of the tumor burden. Approximately 50% of prostate cancers carry a chromosomal translocation resulting in generation of the TMPRSS2-ERG fusion gene, which is unique to the tumor cells of each individual patient because of variability in the fusion breakpoint sites. In the present study, we examined the structural preconditions for TMPRSS2-ERG fusion sites in comparison with mesenchymal tumors in pediatric patients to determine whether the sequence composition is suitable for the establishment of tumor-specific quantification assays in prostate cancer patients. Genomic repeat elements represent potential obstacles to establishment of quantification assays, and we found similar proportions of repeat elements at fusion sites in prostate cancer to those reported for mesenchymal tumors, where genomic fusion sequences are established as biomarkers. Our data support the development of the TMPRSS2-ERG fusion gene as a noninvasive tumor marker for therapy assessment, risk stratification, and relapse detection to improve personalized therapy strategies for patients with prostate cancer.

Authors with CRIS profile

Manuela Krumbholz Department of Paediatrics and Adolescent Medicine Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Robert Stöhr Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Helge Taubert Professur für Molekulare Urologie Bernd Wullich Lehrstuhl für Urologie Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Markus Metzler Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie

Involved external institutions

Universität Regensburg DE Germany (DE)

How to cite

APA:

Krumbholz, M., Agaimy, A., Stöhr, R., Burger, M., Wach, S., Taubert, H.,... Metzler, M. (2019). Molecular Composition of Genomic TMPRSS2-ERG Rearrangements in Prostate Cancer. Disease Markers, 2019. https://doi.org/10.1155/2019/5085373

MLA:

Krumbholz, Manuela, et al. "Molecular Composition of Genomic TMPRSS2-ERG Rearrangements in Prostate Cancer." Disease Markers 2019 (2019).

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