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01-06-2018 | Original Article

Immunohistochemically detected IDH1^R132H mutation is rare and mostly heterogeneous in prostate cancer

Authors: Andrea Hinsch, Meta Brolund, Claudia Hube-Magg, Martina Kluth, Ronald Simon, Christina Möller-Koop, Guido Sauter, Stefan Steurer, Andreas Luebke, Alexander Angerer, Corinna Wittmer, Emily Neubauer, Cosima Göbel, Franziska Büscheck, Sarah Minner, Waldemar Wilczak, Thorsten Schlomm, Frank Jacobsen, Till Sebastian Clauditz, Till Krech, Maria Christina Tsourlakis, Cornelia Schroeder

Published in: World Journal of Urology | Issue 6/2018

Abstract

Background

IDH1 mutations are oncogenic through induction of DNA damage and genome instability. They are of therapeutic interest because they confer increased sensitivity to radiation and cytotoxic therapy and hold potential for vaccination therapy.

Methods

In this study, we analyzed more than 17,000 primary prostate cancer tissues with a mutation-specific antibody for the IDH1^R132H mutation.

Results

IDH1 mutation-specific staining was found in 42 of 15,531 (0.3%) interpretable cancers. IDH1 mutation was associated with higher preoperative PSA and Gleason grade (p < 0.05, each) but was unrelated to PSA recurrence. A comparison with other molecular tumor features available from earlier studies revealed that TMPRSS2-ERG fusion as well as deletion of PTEN, 5q21, 6q15, and 3p13 was less frequent in IDH1-mutated than in non-mutated cancer. Increased lethality of genetically instable, “aberration-rich” cancer cells in the presence of IDH1 mutations could possibly explain this observation. Heterogeneity analysis revealed a homogeneous mutation in only 1 of 16 IDH1-mutated cancers. This high degree of heterogeneity may profoundly limit therapeutic targeting of IDH1 mutations in prostate cancer.

Conclusions

The data show that 0.3% of prostate cancers have an IDH1^R132H mutation and that these are mostly heterogeneous. Once specific anti-IDH1 therapy becomes reality, only a very small group of prostate cancer patients may benefit from such a treatment.

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Title: Immunohistochemically detected IDH1R132H mutation is rare and mostly heterogeneous in prostate cancer
Authors: Andrea Hinsch
Meta Brolund
Claudia Hube-Magg
Martina Kluth
Ronald Simon
Christina Möller-Koop
Guido Sauter
Stefan Steurer
Andreas Luebke
Alexander Angerer
Corinna Wittmer
Emily Neubauer
Cosima Göbel
Franziska Büscheck
Sarah Minner
Waldemar Wilczak
Thorsten Schlomm
Frank Jacobsen
Till Sebastian Clauditz
Till Krech
Maria Christina Tsourlakis
Cornelia Schroeder
Publication date: 01-06-2018
Publisher: Springer Berlin Heidelberg
Published in: World Journal of Urology / Issue 6/2018
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-018-2225-7

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Springer Medicine

Immunohistochemically detected IDH1^R132H mutation is rare and mostly heterogeneous in prostate cancer

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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