Skip to main content
main-content

21.06.2017 | Methods Paper | Ausgabe 5/2017 Open Access

Acta Neuropathologica 5/2017

Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing

Zeitschrift:
Acta Neuropathologica > Ausgabe 5/2017
Autoren:
Philipp Euskirchen, Franck Bielle, Karim Labreche, Wigard P. Kloosterman, Shai Rosenberg, Mailys Daniau, Charlotte Schmitt, Julien Masliah-Planchon, Franck Bourdeaut, Caroline Dehais, Yannick Marie, Jean-Yves Delattre, Ahmed Idbaih
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00401-017-1743-5) contains supplementary material, which is available to authorized users.

Abstract

Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis, and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous system tumors, the current World Health Organization classification explicitly demands molecular testing, e.g., for 1p/19q-codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making. Here, we explored the potential of a pocket-size nanopore sequencing device for multimodal and rapid molecular diagnostics of cancer. Low-pass whole genome sequencing was used to simultaneously generate copy number (CN) and methylation profiles from native tumor DNA in the same sequencing run. Single nucleotide variants in IDH1, IDH2, TP53, H3F3A, and the TERT promoter region were identified using deep amplicon sequencing. Nanopore sequencing yielded ~0.1X genome coverage within 6 h and resulting CN and epigenetic profiles correlated well with matched microarray data. Diagnostically relevant alterations, such as 1p/19q codeletion, and focal amplifications could be recapitulated. Using ad hoc random forests, we could perform supervised pan-cancer classification to distinguish gliomas, medulloblastomas, and brain metastases of different primary sites. Single nucleotide variants in IDH1, IDH2, and H3F3A were identified using deep amplicon sequencing within minutes of sequencing. Detection of TP53 and TERT promoter mutations shows that sequencing of entire genes and GC-rich regions is feasible. Nanopore sequencing allows same-day detection of structural variants, point mutations, and methylation profiling using a single device with negligible capital cost. It outperforms hybridization-based and current sequencing technologies with respect to time to diagnosis and required laboratory equipment and expertise, aiming to make precision medicine possible for every cancer patient, even in resource-restricted settings.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

e.Med Neurologie & Psychiatrie

Kombi-Abonnement

Mit e.Med Neurologie & Psychiatrie erhalten Sie Zugang zu CME-Fortbildungen der Fachgebiete, den Premium-Inhalten der dazugehörigen Fachzeitschriften, inklusive einer gedruckten Zeitschrift Ihrer Wahl.

e.Med Neurologie

Kombi-Abonnement

Mit e.Med Neurologie erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes, den Premium-Inhalten der neurologischen Fachzeitschriften, inklusive einer gedruckten Neurologie-Zeitschrift Ihrer Wahl.

Zusatzmaterial
Supplementary material 1 (PDF 11720 kb)
401_2017_1743_MOESM1_ESM.pdf
Supplementary material 2 (XLSX 38 kb)
401_2017_1743_MOESM2_ESM.xlsx
Supplementary material 3 (XLSX 9 kb)
401_2017_1743_MOESM3_ESM.xlsx
Supplementary material 4 (XLSX 28 kb)
401_2017_1743_MOESM4_ESM.xlsx
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 5/2017

Acta Neuropathologica 5/2017 Zur Ausgabe

Neu im Fachgebiet Pathologie

01.11.2018 | Schwerpunkt: Immunpathologie | Ausgabe 6/2018

Der prädiktive Wert der PD-L1-Diagnostik

22.10.2018 | Schwerpunkt: Immunpathologie | Ausgabe 6/2018

Digitale Pathologie in der Immunonkologie – Aktuelle Chancen und Herausforderungen

Überblick zur Analyse von Immunzellinfiltraten mittels Whole Slide Imaging

22.10.2018 | Schwerpunkt: Immunpathologie | Ausgabe 6/2018

Prognostische Bedeutung von Immunzellinfiltraten in der Tumorpathologie