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Whole Genome Sequencing-Based Discovery of Structural Variants in Glioblastoma

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Glioblastoma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1741))

Abstract

Next-generation DNA sequencing (NGS) technologies are currently being applied in both research and clinical settings for the understanding and management of disease. The goal is to use high-throughput sequencing to identify specific variants that drive tumorigenesis within each individual’s tumor genomic profile. The significance of copy number and structural variants in glioblastoma makes it essential to broaden the search beyond oncogenic single nucleotide variants toward whole genome profiles of genetic aberrations that may contribute to disease progression. The heterogeneity of glioblastoma and its variability of cancer driver mutations necessitate a more robust examination of a patient’s tumor genome. Here, we present patient whole genome sequencing (WGS) information to identify oncogenic structural variants that may contribute to glioblastoma pathogenesis. We provide WGS protocols and bioinformatics approaches to identify copy number and structural variations in 41 glioblastoma patient samples. We present how WGS can identify structural diversity within glioblastoma samples. We specifically show how to apply current bioinformatics tools to detect EGFR variants and other structural aberrations from DNA whole genome sequencing and how to validate those variants within the laboratory. These comprehensive WGS protocols can provide additional information directing more precise therapeutic options in the treatment of glioblastoma.

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Acknowledgments

We greatly thank all patients for their consent and donation of tissue specimens for this work.

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    Authors and Affiliations

    1. New York Genome Center, New York, NY, USA

      Kazimierz O. Wrzeszczynski, Vanessa Felice, Minita Shah, Sadia Rahman, Anne-Katrin Emde, Vaidehi Jobanputra & Robert B. Darnell

    2. Columbia University Medical Center, New York, NY, USA

      Vaidehi Jobanputra

    3. Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, NY, USA

      Mayu O. Frank & Robert B. Darnell

    4. Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA

      Robert B. Darnell

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    1. Kazimierz O. Wrzeszczynski
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    Correspondence to Kazimierz O. Wrzeszczynski .

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    1. Department of Neurosurgery, NYU School of Medicine, New York, New York, USA

      Dimitris G. Placantonakis

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    Wrzeszczynski, K.O. et al. (2018). Whole Genome Sequencing-Based Discovery of Structural Variants in Glioblastoma. In: Placantonakis, D. (eds) Glioblastoma. Methods in Molecular Biology, vol 1741. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7659-1_1

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    • DOI: https://doi.org/10.1007/978-1-4939-7659-1_1

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    • Publisher Name: Humana Press, New York, NY

    • Print ISBN: 978-1-4939-7658-4

    • Online ISBN: 978-1-4939-7659-1

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