TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer

Stefan Steurer; Pascale Sophia Mayer; Meike Adam; Antje Krohn; Christina Koop; Daniel Ospina-Klinck; Ali Attarchi Tehrani; Ronald Simon; Pierre Tennstedt; Markus Graefen; Corinna Wittmer; Benedikt Brors; Christoph Plass; Jan Korbel; Joachim Weischenfeldt; Guido Sauter; Hartwig Huland; Maria Christina Tsourlakis; Sarah Minner; Thorsten Schlomm

doi:10.1016/j.eururo.2014.06.027

TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer

Stefan Steurer, Pascale Sophia Mayer, Meike Adam, Antje Krohn, Christina Koop, Daniel Ospina-Klinck, Ali Attarchi Tehrani, Ronald Simon, Pierre Tennstedt, Markus Graefen, Corinna Wittmer, Benedikt Brors, Christoph Plass, Jan Korbel, Joachim Weischenfeldt, Guido Sauter, Hartwig Huland, Maria Christina Tsourlakis, Sarah Minner, Thorsten Schlomm

43 Citations (Scopus)

Abstract

Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes-such as transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11,152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2-ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3+4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non-androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients.

Original language	English
Journal	European Urology (Italian Edition)
Volume	66
Issue number	6
Pages (from-to)	978-81
Number of pages	4
ISSN	1828-6569
DOIs	https://doi.org/10.1016/j.eururo.2014.06.027
Publication status	Published - 1 Dec 2014
Externally published	Yes

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Steurer, S., Mayer, P. S., Adam, M., Krohn, A., Koop, C., Ospina-Klinck, D., Tehrani, A. A., Simon, R., Tennstedt, P., Graefen, M., Wittmer, C., Brors, B., Plass, C., Korbel, J., Weischenfeldt, J., Sauter, G., Huland, H., Tsourlakis, M. C., Minner, S., & Schlomm, T. (2014). TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer. European Urology (Italian Edition), 66(6), 978-81. https://doi.org/10.1016/j.eururo.2014.06.027

Steurer, S, Mayer, PS, Adam, M, Krohn, A, Koop, C, Ospina-Klinck, D, Tehrani, AA, Simon, R, Tennstedt, P, Graefen, M, Wittmer, C, Brors, B, Plass, C, Korbel, J, Weischenfeldt, J, Sauter, G, Huland, H, Tsourlakis, MC, Minner, S & Schlomm, T 2014, 'TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer', European Urology (Italian Edition), vol. 66, no. 6, pp. 978-81. https://doi.org/10.1016/j.eururo.2014.06.027

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title = "TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer",

abstract = "Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes-such as transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11,152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2-ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3+4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non-androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients.",

author = "Stefan Steurer and Mayer, {Pascale Sophia} and Meike Adam and Antje Krohn and Christina Koop and Daniel Ospina-Klinck and Tehrani, {Ali Attarchi} and Ronald Simon and Pierre Tennstedt and Markus Graefen and Corinna Wittmer and Benedikt Brors and Christoph Plass and Jan Korbel and Joachim Weischenfeldt and Guido Sauter and Hartwig Huland and Tsourlakis, {Maria Christina} and Sarah Minner and Thorsten Schlomm",

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doi = "10.1016/j.eururo.2014.06.027",

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T1 - TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer

AU - Steurer, Stefan

AU - Mayer, Pascale Sophia

AU - Adam, Meike

AU - Krohn, Antje

AU - Koop, Christina

AU - Ospina-Klinck, Daniel

AU - Tehrani, Ali Attarchi

AU - Simon, Ronald

AU - Tennstedt, Pierre

AU - Graefen, Markus

AU - Wittmer, Corinna

AU - Brors, Benedikt

AU - Plass, Christoph

AU - Korbel, Jan

AU - Weischenfeldt, Joachim

AU - Sauter, Guido

AU - Huland, Hartwig

AU - Tsourlakis, Maria Christina

AU - Minner, Sarah

AU - Schlomm, Thorsten

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes-such as transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11,152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2-ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3+4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non-androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients.

AB - Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes-such as transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11,152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2-ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3+4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non-androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients.

U2 - 10.1016/j.eururo.2014.06.027

DO - 10.1016/j.eururo.2014.06.027

M3 - Journal article

C2 - 25015038

SN - 1828-6569

VL - 66

SP - 978

EP - 981

JO - European Urology (Italian Edition)

JF - European Urology (Italian Edition)

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