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Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma

Malignant peripheral nerve sheath tumors (MPNST) are the deadliest cancer that arises in individuals diagnosed with neurofibromatosis and account for nearly 5% of the 15,000 soft tissue sarcomas diagnosed in the United States each year. Comprised of neoplastic Schwann cells, primary risk factors for...

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Autores principales: Mattox, Austin K, Douville, Christopher, Silliman, Natalie, Ptak, Janine, Dobbyn, Lisa, Schaefer, Joy, Popoli, Maria, Blair, Cherie, Judge, Kathy, Pollard, Kai, Pratilas, Christine, Blakeley, Jaishri, Rodriguez, Fausto, Papadopoulos, Nickolas, Belzberg, Allan, Bettegowda, Chetan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094745/
https://www.ncbi.nlm.nih.gov/pubmed/35244537
http://dx.doi.org/10.7554/eLife.74238
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author Mattox, Austin K
Douville, Christopher
Silliman, Natalie
Ptak, Janine
Dobbyn, Lisa
Schaefer, Joy
Popoli, Maria
Blair, Cherie
Judge, Kathy
Pollard, Kai
Pratilas, Christine
Blakeley, Jaishri
Rodriguez, Fausto
Papadopoulos, Nickolas
Belzberg, Allan
Bettegowda, Chetan
author_facet Mattox, Austin K
Douville, Christopher
Silliman, Natalie
Ptak, Janine
Dobbyn, Lisa
Schaefer, Joy
Popoli, Maria
Blair, Cherie
Judge, Kathy
Pollard, Kai
Pratilas, Christine
Blakeley, Jaishri
Rodriguez, Fausto
Papadopoulos, Nickolas
Belzberg, Allan
Bettegowda, Chetan
author_sort Mattox, Austin K
collection PubMed
description Malignant peripheral nerve sheath tumors (MPNST) are the deadliest cancer that arises in individuals diagnosed with neurofibromatosis and account for nearly 5% of the 15,000 soft tissue sarcomas diagnosed in the United States each year. Comprised of neoplastic Schwann cells, primary risk factors for developing MPNST include existing plexiform neurofibromas (PN), prior radiotherapy treatment, and expansive germline mutations involving the entire NF1 gene and surrounding genes. PN develop in nearly 30–50% of patients with neurofibromatosis type 1 (NF1) and most often grow rapidly in the first decade of life. One of the most important aspects of clinical care for NF1 patients is monitoring PN for signs of malignant transformation to MPNST that occurs in 10–15% of patients. We perform aneuploidy analysis on ctDNA from 883 ostensibly healthy individuals and 28 patients with neurofibromas, including 7 patients with benign neurofibroma, 9 patients with PN and 12 patients with MPNST. Overall sensitivity for detecting MPNST using genome wide aneuploidy scoring was 33%, and analysis of sub-chromosomal copy number alterations (CNAs) improved sensitivity to 50% while retaining a high specificity of 97%. In addition, we performed mutation analysis on plasma cfDNA for a subset of patients and identified mutations in NF1, NF2, RB1, TP53BP2, and GOLGA2. Given the high throughput and relatively low sequencing coverage required by our assay, liquid biopsy represents a promising technology to identify incipient MPNST.
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spelling pubmed-90947452022-05-12 Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma Mattox, Austin K Douville, Christopher Silliman, Natalie Ptak, Janine Dobbyn, Lisa Schaefer, Joy Popoli, Maria Blair, Cherie Judge, Kathy Pollard, Kai Pratilas, Christine Blakeley, Jaishri Rodriguez, Fausto Papadopoulos, Nickolas Belzberg, Allan Bettegowda, Chetan eLife Cancer Biology Malignant peripheral nerve sheath tumors (MPNST) are the deadliest cancer that arises in individuals diagnosed with neurofibromatosis and account for nearly 5% of the 15,000 soft tissue sarcomas diagnosed in the United States each year. Comprised of neoplastic Schwann cells, primary risk factors for developing MPNST include existing plexiform neurofibromas (PN), prior radiotherapy treatment, and expansive germline mutations involving the entire NF1 gene and surrounding genes. PN develop in nearly 30–50% of patients with neurofibromatosis type 1 (NF1) and most often grow rapidly in the first decade of life. One of the most important aspects of clinical care for NF1 patients is monitoring PN for signs of malignant transformation to MPNST that occurs in 10–15% of patients. We perform aneuploidy analysis on ctDNA from 883 ostensibly healthy individuals and 28 patients with neurofibromas, including 7 patients with benign neurofibroma, 9 patients with PN and 12 patients with MPNST. Overall sensitivity for detecting MPNST using genome wide aneuploidy scoring was 33%, and analysis of sub-chromosomal copy number alterations (CNAs) improved sensitivity to 50% while retaining a high specificity of 97%. In addition, we performed mutation analysis on plasma cfDNA for a subset of patients and identified mutations in NF1, NF2, RB1, TP53BP2, and GOLGA2. Given the high throughput and relatively low sequencing coverage required by our assay, liquid biopsy represents a promising technology to identify incipient MPNST. eLife Sciences Publications, Ltd 2022-03-04 /pmc/articles/PMC9094745/ /pubmed/35244537 http://dx.doi.org/10.7554/eLife.74238 Text en © 2022, Mattox et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Mattox, Austin K
Douville, Christopher
Silliman, Natalie
Ptak, Janine
Dobbyn, Lisa
Schaefer, Joy
Popoli, Maria
Blair, Cherie
Judge, Kathy
Pollard, Kai
Pratilas, Christine
Blakeley, Jaishri
Rodriguez, Fausto
Papadopoulos, Nickolas
Belzberg, Allan
Bettegowda, Chetan
Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma
title Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma
title_full Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma
title_fullStr Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma
title_full_unstemmed Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma
title_short Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma
title_sort detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094745/
https://www.ncbi.nlm.nih.gov/pubmed/35244537
http://dx.doi.org/10.7554/eLife.74238
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