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Open AccessFeature PaperCommunication

Genomics of MPNST (GeM) Consortium: Rationale and Study Design for Multi-Omic Characterization of NF1-Associated and Sporadic MPNSTs

1
Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA 02115, USA
2
European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, UK
3
Department of Pathology, University College London Cancer Institute, Bloomsbury, London WC1E 6BT, UK
4
Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex HA7 4LP, UK
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Oncology Division, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
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Department of Pathology, New York University Langone Health, New York City, NY 10016, USA
7
Department of Pathology, Moffitt Cancer Center, Tampa, FL 33612, USA
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Department of Pathology, Boston Children’s Hospital, Boston, MA 02115, USA
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Department of Pathology and Laboratory Medicine, Mt. Sinai Hospital, Toronto, ON M5G 1XF, Canada
10
Department of Pathology, Lifespan Laboratories, Rhode Island Hospital, Providence, RI 02903, USA
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Departments of Orthopaedics and Oncological Sciences; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
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Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, MA 02114, USA
13
Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2C1, Canada
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Department of Rehabilitation, Nagoya University Hospital, Nagoya 466-8550, Aichi, Japan
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Department of Neurology, Boston Children’s Hospital, Boston, MA 02115, USA
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GeneHome, Moffitt Cancer Center, Tampa, FL 33612, USA
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Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
Genes 2020, 11(4), 387; https://doi.org/10.3390/genes11040387
Received: 10 March 2020 / Accepted: 31 March 2020 / Published: 2 April 2020
(This article belongs to the Special Issue Genomics and Models of Nerve Sheath Tumors)
The Genomics of Malignant Peripheral Nerve Sheath Tumor (GeM) Consortium is an international collaboration focusing on multi-omic analysis of malignant peripheral nerve sheath tumors (MPNSTs), the most aggressive tumor associated with neurofibromatosis type 1 (NF1). Here we present a summary of current knowledge gaps, a description of our consortium and the cohort we have assembled, and an overview of our plans for multi-omic analysis of these tumors. We propose that our analysis will lead to a better understanding of the order and timing of genetic events related to MPNST initiation and progression. Our ten institutions have assembled 96 fresh frozen NF1-related (63%) and sporadic MPNST specimens from 86 subjects with corresponding clinical and pathological data. Clinical data have been collected as part of the International MPNST Registry. We will characterize these tumors with bulk whole genome sequencing, RNAseq, and DNA methylation profiling. In addition, we will perform multiregional analysis and temporal sampling, with the same methodologies, on a subset of nine subjects with NF1-related MPNSTs to assess tumor heterogeneity and cancer evolution. Subsequent multi-omic analyses of additional archival specimens will include deep exome sequencing (500×) and high density copy number arrays for both validation of results based on fresh frozen tumors, and to assess further tumor heterogeneity and evolution. Digital pathology images are being collected in a cloud-based platform for consensus review. The result of these efforts will be the largest MPNST multi-omic dataset with correlated clinical and pathological information ever assembled. View Full-Text
Keywords: genomics; MPNST; tumor evolution; neurofibromatosis; pathology; next generation sequencing; clinical genetics genomics; MPNST; tumor evolution; neurofibromatosis; pathology; next generation sequencing; clinical genetics
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Miller, D.T.; Cortés-Ciriano, I.; Pillay, N.; Hirbe, A.C.; Snuderl, M.; Bui, M.M.; Piculell, K.; Al-Ibraheemi, A.; Dickson, B.C.; Hart, J.; Jones, K.; Jordan, J.T.; Kim, R.H.; Lindsay, D.; Nishida, Y.; Ullrich, N.J.; Wang, X.; Park, P.J.; Flanagan, A.M., on behalf of the Genomics of MPNST (GeM) Consortium; Genomics of MPNST (GeM) Consortium: Rationale and Study Design for Multi-Omic Characterization of NF1-Associated and Sporadic MPNSTs. Genes 2020, 11, 387.

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