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Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets

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Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets. / Sahm, Felix; Schrimpf, Daniel; Jones, David T W; Meyer, Jochen; Kratz, Annekathrin; Reuss, David; Capper, David; Koelsche, Christian; Korshunov, Andrey; Wiestler, Benedikt; Buchhalter, Ivo; Milde, Till; Selt, Florian; Sturm, Dominik; Kool, Marcel; Hummel, Manuela; Bewerunge-Hudler, Melanie; Mawrin, Christian; Schüller, Ulrich; Jungk, Christine; Wick, Antje; Witt, Olaf; Platten, Michael; Herold-Mende, Christel; Unterberg, Andreas; Pfister, Stefan M; Wick, Wolfgang; Deimling, Andreas.

in: ACTA NEUROPATHOL, Jahrgang 131, Nr. 6, 06.2016, S. 903-10.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Sahm, F, Schrimpf, D, Jones, DTW, Meyer, J, Kratz, A, Reuss, D, Capper, D, Koelsche, C, Korshunov, A, Wiestler, B, Buchhalter, I, Milde, T, Selt, F, Sturm, D, Kool, M, Hummel, M, Bewerunge-Hudler, M, Mawrin, C, Schüller, U, Jungk, C, Wick, A, Witt, O, Platten, M, Herold-Mende, C, Unterberg, A, Pfister, SM, Wick, W & Deimling, A 2016, 'Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets', ACTA NEUROPATHOL, Jg. 131, Nr. 6, S. 903-10. https://doi.org/10.1007/s00401-015-1519-8

APA

Sahm, F., Schrimpf, D., Jones, D. T. W., Meyer, J., Kratz, A., Reuss, D., Capper, D., Koelsche, C., Korshunov, A., Wiestler, B., Buchhalter, I., Milde, T., Selt, F., Sturm, D., Kool, M., Hummel, M., Bewerunge-Hudler, M., Mawrin, C., Schüller, U., ... Deimling, A. (2016). Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets. ACTA NEUROPATHOL, 131(6), 903-10. https://doi.org/10.1007/s00401-015-1519-8

Vancouver

Sahm F, Schrimpf D, Jones DTW, Meyer J, Kratz A, Reuss D et al. Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets. ACTA NEUROPATHOL. 2016 Jun;131(6):903-10. https://doi.org/10.1007/s00401-015-1519-8

Bibtex

@article{2cacab09cd074748a6213765b4f4182c,
title = "Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets",
abstract = "With the number of prognostic and predictive genetic markers in neuro-oncology steadily growing, the need for comprehensive molecular analysis of neuropathology samples has vastly increased. We therefore developed a customized enrichment/hybrid-capture-based next-generation sequencing (NGS) gene panel comprising the entire coding and selected intronic and promoter regions of 130 genes recurrently altered in brain tumors, allowing for the detection of single nucleotide variations, fusions, and copy number aberrations. Optimization of probe design, library generation and sequencing conditions on 150 samples resulted in a 5-workday routine workflow from the formalin-fixed paraffin-embedded sample to neuropathological report. This protocol was applied to 79 retrospective cases with established molecular aberrations for validation and 71 prospective cases for discovery of potential therapeutic targets. Concordance of NGS compared to established, single biomarker methods was 98.0 %, with discrepancies resulting from one case where a TERT promoter mutation was not called by NGS and three ATRX mutations not being detected by Sanger sequencing. Importantly, in samples with low tumor cell content, NGS was able to identify mutant alleles that were not detectable by traditional methods. Information derived from NGS data identified potential targets for experimental therapy in 37/47 (79 %) glioblastomas, 9/10 (90 %) pilocytic astrocytomas, and 5/14 (36 %) medulloblastomas in the prospective target discovery cohort. In conclusion, we present the settings for high-throughput, adaptive next-generation sequencing in routine neuropathology diagnostics. Such an approach will likely become highly valuable in the near future for treatment decision making, as more therapeutic targets emerge and genetic information enters the classification of brain tumors.",
keywords = "Journal Article",
author = "Felix Sahm and Daniel Schrimpf and Jones, {David T W} and Jochen Meyer and Annekathrin Kratz and David Reuss and David Capper and Christian Koelsche and Andrey Korshunov and Benedikt Wiestler and Ivo Buchhalter and Till Milde and Florian Selt and Dominik Sturm and Marcel Kool and Manuela Hummel and Melanie Bewerunge-Hudler and Christian Mawrin and Ulrich Sch{\"u}ller and Christine Jungk and Antje Wick and Olaf Witt and Michael Platten and Christel Herold-Mende and Andreas Unterberg and Pfister, {Stefan M} and Wolfgang Wick and Andreas Deimling",
year = "2016",
month = jun,
doi = "10.1007/s00401-015-1519-8",
language = "English",
volume = "131",
pages = "903--10",
journal = "ACTA NEUROPATHOL",
issn = "0001-6322",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets

AU - Sahm, Felix

AU - Schrimpf, Daniel

AU - Jones, David T W

AU - Meyer, Jochen

AU - Kratz, Annekathrin

AU - Reuss, David

AU - Capper, David

AU - Koelsche, Christian

AU - Korshunov, Andrey

AU - Wiestler, Benedikt

AU - Buchhalter, Ivo

AU - Milde, Till

AU - Selt, Florian

AU - Sturm, Dominik

AU - Kool, Marcel

AU - Hummel, Manuela

AU - Bewerunge-Hudler, Melanie

AU - Mawrin, Christian

AU - Schüller, Ulrich

AU - Jungk, Christine

AU - Wick, Antje

AU - Witt, Olaf

AU - Platten, Michael

AU - Herold-Mende, Christel

AU - Unterberg, Andreas

AU - Pfister, Stefan M

AU - Wick, Wolfgang

AU - Deimling, Andreas

PY - 2016/6

Y1 - 2016/6

N2 - With the number of prognostic and predictive genetic markers in neuro-oncology steadily growing, the need for comprehensive molecular analysis of neuropathology samples has vastly increased. We therefore developed a customized enrichment/hybrid-capture-based next-generation sequencing (NGS) gene panel comprising the entire coding and selected intronic and promoter regions of 130 genes recurrently altered in brain tumors, allowing for the detection of single nucleotide variations, fusions, and copy number aberrations. Optimization of probe design, library generation and sequencing conditions on 150 samples resulted in a 5-workday routine workflow from the formalin-fixed paraffin-embedded sample to neuropathological report. This protocol was applied to 79 retrospective cases with established molecular aberrations for validation and 71 prospective cases for discovery of potential therapeutic targets. Concordance of NGS compared to established, single biomarker methods was 98.0 %, with discrepancies resulting from one case where a TERT promoter mutation was not called by NGS and three ATRX mutations not being detected by Sanger sequencing. Importantly, in samples with low tumor cell content, NGS was able to identify mutant alleles that were not detectable by traditional methods. Information derived from NGS data identified potential targets for experimental therapy in 37/47 (79 %) glioblastomas, 9/10 (90 %) pilocytic astrocytomas, and 5/14 (36 %) medulloblastomas in the prospective target discovery cohort. In conclusion, we present the settings for high-throughput, adaptive next-generation sequencing in routine neuropathology diagnostics. Such an approach will likely become highly valuable in the near future for treatment decision making, as more therapeutic targets emerge and genetic information enters the classification of brain tumors.

AB - With the number of prognostic and predictive genetic markers in neuro-oncology steadily growing, the need for comprehensive molecular analysis of neuropathology samples has vastly increased. We therefore developed a customized enrichment/hybrid-capture-based next-generation sequencing (NGS) gene panel comprising the entire coding and selected intronic and promoter regions of 130 genes recurrently altered in brain tumors, allowing for the detection of single nucleotide variations, fusions, and copy number aberrations. Optimization of probe design, library generation and sequencing conditions on 150 samples resulted in a 5-workday routine workflow from the formalin-fixed paraffin-embedded sample to neuropathological report. This protocol was applied to 79 retrospective cases with established molecular aberrations for validation and 71 prospective cases for discovery of potential therapeutic targets. Concordance of NGS compared to established, single biomarker methods was 98.0 %, with discrepancies resulting from one case where a TERT promoter mutation was not called by NGS and three ATRX mutations not being detected by Sanger sequencing. Importantly, in samples with low tumor cell content, NGS was able to identify mutant alleles that were not detectable by traditional methods. Information derived from NGS data identified potential targets for experimental therapy in 37/47 (79 %) glioblastomas, 9/10 (90 %) pilocytic astrocytomas, and 5/14 (36 %) medulloblastomas in the prospective target discovery cohort. In conclusion, we present the settings for high-throughput, adaptive next-generation sequencing in routine neuropathology diagnostics. Such an approach will likely become highly valuable in the near future for treatment decision making, as more therapeutic targets emerge and genetic information enters the classification of brain tumors.

KW - Journal Article

U2 - 10.1007/s00401-015-1519-8

DO - 10.1007/s00401-015-1519-8

M3 - SCORING: Journal article

C2 - 26671409

VL - 131

SP - 903

EP - 910

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 6

ER -