@article{014c32f816b64ce097667d36ea7f4fec,
title = "Genomics of mpnst (Gem) consortium: Rationale and study design for multi-omic characterization of nf1-associated and sporadic mpnsts",
abstract = "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.",
keywords = "Clinical genetics, Genomics, MPNST, Neurofibromatosis, Next generation sequencing, Pathology, Tumor evolution",
author = "Miller, {David T.} and Isidro Cort{\'e}s-Ciriano and Nischalan Pillay and Hirbe, {Angela C.} and Matija Snuderl and Bui, {Marilyn M.} and Katherine Piculell and Alyaa Al-Ibraheemi and Dickson, {Brendan C.} and Jesse Hart and Kevin Jones and Jordan, {Justin T.} and Kim, {Raymond H.} and Daniel Lindsay and Yoshihiro Nishida and Ullrich, {Nicole J.} and Xia Wang and Park, {Peter J.} and Flanagan, {Adrienne M.}",
note = "Funding Information: Funding: This research was primarily funded by the Neurofibromatosis Research Initiative (NFRI) at Boston Children{\textquoteright}s Hospital, made possible by an anonymous donation. N.P. is a Cancer Research UK clinician scientist, grant number 18387. A.M.F is a NIHR senior investigator; A.M.F., and N.P. are supported by the UK Department of Health{\textquoteright}s National Institute for Health Research, UCLH Biomedical Research Centre and by UCL Experimental Cancer Centre. Biobanking of U.K. patient samples was funded by the Research and Development Office of the RNOH. The methylation profiling program at NYU Langone Health has been supported by the Friedberg Charitable Foundation, the Sohn Foundation and the Making Headway Foundation (to M.S.). R.H.K. was supported by the Bhalwani Family Charitable Foundation Acknowledgments: Sample identification and processing was supported by several individuals and core facilities, including: Sam Cano and Tamara Restrepo in the Laboratory for Advanced Molecular Pediatric Pathology (LaMPP) and Umesh Paneru in Histology at Boston Children{\textquoteright}s Hospital; Maia Roche in the Department of Histopathology at Royal National Orthopaedic Hospital; Anthony Griffin and Nalan Gokgoz at Mt. Sinai Hospital; the Collaborative Data Services Core, Tissue Core and Analytic Microscopy Core Facilities at the H. Lee Moffitt Cancer Center & Research Institute, an NCI designated Comprehensive Cancer Center (P30-CA076292); Diane Lucente, Alexandra Silva, and James Gusella at Massachusetts General Hospital; Jacqueline Hart and David Viskochil at Huntsman Cancer Institute; Sonika Dahiya and Vanessa Eulo at Washington University School of Medicine. We also thank Sarah Berns and Diane Shao at Boston Children{\textquoteright}s Hospital for help preparing an early outline of the manuscript. Administrative and regulatory support for the Coordinating Center was provided by Jacqueline Breen, Tyson Heilhecker, Noah McClanan, Sara Soto, and Tim Linkkila at Boston Children{\textquoteright}s Hospital. Funding Information: This research was primarily funded by the Neurofibromatosis Research Initiative (NFRI) at Boston Children?s Hospital, made possible by an anonymous donation. N.P. is a Cancer Research UK clinician scientist, grant number 18387. A.M.F is a NIHR senior investigator; A.M.F., and N.P. are supported by the UK Department of Health?s National Institute for Health Research, UCLH Biomedical Research Centre and by UCL Experimental Cancer Centre. Biobanking of U.K. patient samples was funded by the Research and Development Office of the RNOH. The methylation profiling program at NYU Langone Health has been supported by the Friedberg Charitable Foundation, the Sohn Foundation and the Making Headway Foundation (to M.S.). R.H.K. was supported by the Bhalwani Family Charitable Foundation. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = apr,
doi = "10.3390/genes11040387",
language = "English",
volume = "11",
journal = "Genes",
issn = "2073-4425",
number = "4",
}