Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

Clarissa Gerhauser; Francesco Favero; Thomas Risch; Ronald Simon; Lars Feuerbach; Yassen Assenov; Doreen Heckmann; Nikos Sidiropoulos; Sebastian M Waszak; Daniel Hübschmann; Alfonso Urbanucci; Etsehiwot G Girma; Vladimir Kuryshev; Leszek J Klimczak; Natalie Saini; Adrian M Stütz; Dieter Weichenhan; Lisa-Marie Böttcher; Reka Toth; Josephine D Hendriksen; Christina Koop; Pavlo Lutsik; Sören Matzk; Hans-Jörg Warnatz; Vyacheslav Amstislavskiy; Clarissa Feuerstein; Benjamin Raeder; Olga Bogatyrova; Eva-Maria Schmitz; Claudia Hube-Magg; Martina Kluth; Hartwig Huland; Markus Graefen; Chris Lawerenz; Gervaise H Henry; Takafumi N Yamaguchi; Alicia Malewska; Jan Meiners; Daniela Schilling; Eva Reisinger; Roland Eils; Matthias Schlesner; Douglas W Strand; Robert G Bristow; Paul C Boutros; Christof von Kalle; Dmitry Gordenin; Holger Sültmann; Benedikt Brors; Guido Sauter; Christoph Plass; Marie-Laure Yaspo; Jan O Korbel; Thorsten Schlomm; Joachim Weischenfeldt

doi:10.1016/j.ccell.2018.10.016

Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

Clarissa Gerhauser, Francesco Favero, Thomas Risch, Ronald Simon, Lars Feuerbach, Yassen Assenov, Doreen Heckmann, Nikos Sidiropoulos, Sebastian M Waszak, Daniel Hübschmann, Alfonso Urbanucci, Etsehiwot G Girma, Vladimir Kuryshev, Leszek J Klimczak, Natalie Saini, Adrian M Stütz, Dieter Weichenhan, Lisa-Marie Böttcher, Reka Toth, Josephine D HendriksenChristina Koop, Pavlo Lutsik, Sören Matzk, Hans-Jörg Warnatz, Vyacheslav Amstislavskiy, Clarissa Feuerstein, Benjamin Raeder, Olga Bogatyrova, Eva-Maria Schmitz, Claudia Hube-Magg, Martina Kluth, Hartwig Huland, Markus Graefen, Chris Lawerenz, Gervaise H Henry, Takafumi N Yamaguchi, Alicia Malewska, Jan Meiners, Daniela Schilling, Eva Reisinger, Roland Eils, Matthias Schlesner, Douglas W Strand, Robert G Bristow, Paul C Boutros, Christof von Kalle, Dmitry Gordenin, Holger Sültmann, Benedikt Brors, Guido Sauter, Christoph Plass, Marie-Laure Yaspo, Jan O Korbel, Thorsten Schlomm, Joachim Weischenfeldt

224 Citationer (Scopus)

Abstract

Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples.

Originalsprog	Engelsk
Tidsskrift	Cancer Cell
Vol/bind	34
Udgave nummer	6
Sider (fra-til)	996-1011.e8
ISSN	1535-6108
DOI	https://doi.org/10.1016/j.ccell.2018.10.016
Status	Udgivet - 10 dec. 2018

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Gerhauser, C., Favero, F., Risch, T., Simon, R., Feuerbach, L., Assenov, Y., Heckmann, D., Sidiropoulos, N., Waszak, S. M., Hübschmann, D., Urbanucci, A., Girma, E. G., Kuryshev, V., Klimczak, L. J., Saini, N., Stütz, A. M., Weichenhan, D., Böttcher, L.-M., Toth, R., ... Weischenfeldt, J. (2018). Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories. Cancer Cell, 34(6), 996-1011.e8. https://doi.org/10.1016/j.ccell.2018.10.016

Gerhauser, C, Favero, F, Risch, T, Simon, R, Feuerbach, L, Assenov, Y, Heckmann, D, Sidiropoulos, N, Waszak, SM, Hübschmann, D, Urbanucci, A, Girma, EG, Kuryshev, V, Klimczak, LJ, Saini, N, Stütz, AM, Weichenhan, D, Böttcher, L-M, Toth, R, Hendriksen, JD, Koop, C, Lutsik, P, Matzk, S, Warnatz, H-J, Amstislavskiy, V, Feuerstein, C, Raeder, B, Bogatyrova, O, Schmitz, E-M, Hube-Magg, C, Kluth, M, Huland, H, Graefen, M, Lawerenz, C, Henry, GH, Yamaguchi, TN, Malewska, A, Meiners, J, Schilling, D, Reisinger, E, Eils, R, Schlesner, M, Strand, DW, Bristow, RG, Boutros, PC, von Kalle, C, Gordenin, D, Sültmann, H, Brors, B, Sauter, G, Plass, C, Yaspo, M-L, Korbel, JO, Schlomm, T & Weischenfeldt, J 2018, 'Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories', Cancer Cell, bind 34, nr. 6, s. 996-1011.e8. https://doi.org/10.1016/j.ccell.2018.10.016

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title = "Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories",

abstract = "Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples.",

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AU - Gerhauser, Clarissa

AU - Favero, Francesco

AU - Risch, Thomas

AU - Simon, Ronald

AU - Feuerbach, Lars

AU - Assenov, Yassen

AU - Heckmann, Doreen

AU - Sidiropoulos, Nikos

AU - Waszak, Sebastian M

AU - Hübschmann, Daniel

AU - Urbanucci, Alfonso

AU - Girma, Etsehiwot G

AU - Kuryshev, Vladimir

AU - Klimczak, Leszek J

AU - Saini, Natalie

AU - Stütz, Adrian M

AU - Weichenhan, Dieter

AU - Böttcher, Lisa-Marie

AU - Toth, Reka

AU - Hendriksen, Josephine D

AU - Koop, Christina

AU - Lutsik, Pavlo

AU - Matzk, Sören

AU - Warnatz, Hans-Jörg

AU - Amstislavskiy, Vyacheslav

AU - Feuerstein, Clarissa

AU - Raeder, Benjamin

AU - Bogatyrova, Olga

AU - Schmitz, Eva-Maria

AU - Hube-Magg, Claudia

AU - Kluth, Martina

AU - Huland, Hartwig

AU - Graefen, Markus

AU - Lawerenz, Chris

AU - Henry, Gervaise H

AU - Yamaguchi, Takafumi N

AU - Malewska, Alicia

AU - Meiners, Jan

AU - Schilling, Daniela

AU - Reisinger, Eva

AU - Eils, Roland

AU - Schlesner, Matthias

AU - Strand, Douglas W

AU - Bristow, Robert G

AU - Boutros, Paul C

AU - von Kalle, Christof

AU - Gordenin, Dmitry

AU - Sültmann, Holger

AU - Brors, Benedikt

AU - Sauter, Guido

AU - Plass, Christoph

AU - Yaspo, Marie-Laure

AU - Korbel, Jan O

AU - Schlomm, Thorsten

AU - Weischenfeldt, Joachim

PY - 2018/12/10

Y1 - 2018/12/10

N2 - Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples.

AB - Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples.

UR - https://www.scopus.com/pages/publications/85057262396

U2 - 10.1016/j.ccell.2018.10.016

DO - 10.1016/j.ccell.2018.10.016

M3 - Journal article

C2 - 30537516

SN - 1535-6108

VL - 34

SP - 996-1011.e8

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

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