Data from Early Detection of Malignant and Premalignant Peripheral Nerve Tumors Using Cell-Free DNA Fragmentomics Article Swipe
R. Taylor Sundby
,
Jeffrey J. Szymanski
,
Alexander Pan
,
Paul A. Jones
,
Sana Mahmood
,
Olivia H. Reid
,
Divya Srihari
,
Amy E. Armstrong
,
Stacey Chamberlain
,
Sanita Burgic
,
Kara Weekley
,
Béga Murray
,
S. G. Patel
,
Faridi Qaium
,
Andrea N. Lucas
,
Margaret Fagan
,
Anne Dufek
,
Christian F. Meyer
,
Natalie B. Collins
,
Christine A. Pratilas
,
Eva Dombi
,
Andrea M. Gross
,
AeRang Kim
,
John S.A. Chrisinger
,
Carina Dehner
,
Brigitte C. Widemann
,
Angela C. Hirbe
,
Aadel A. Chaudhuri
,
Jack F. Shern
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.c.7474432
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.c.7474432
Purpose:Early detection of neurofibromatosis type 1 (NF1)–associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1.Experimental Design:cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end motifs, and fragment non-negative matrix factorization signatures.Results:The novel cohort of patients with NF1 validated that our previous cfDNA copy-number alteration–based approach identifies malignant PNST (MPNST) but cannot distinguish between benign and premalignant states. Fragmentomic methods were able to differentiate premalignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management.Conclusions:Novel cfDNA fragmentomic signatures distinguish AN from benign plexiform neurofibromas and MPNST, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant PNST in NF1 and provides a blueprint for decentralizing noninvasive cancer surveillance in hereditary cancer predisposition syndromes.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1158/1078-0432.c.7474432
- OA Status
- gold
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4403042999
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4403042999Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/1078-0432.c.7474432Digital Object Identifier
- Title
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Data from Early Detection of Malignant and Premalignant Peripheral Nerve Tumors Using Cell-Free DNA FragmentomicsWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-10-01Full publication date if available
- Authors
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R. Taylor Sundby, Jeffrey J. Szymanski, Alexander Pan, Paul A. Jones, Sana Mahmood, Olivia H. Reid, Divya Srihari, Amy E. Armstrong, Stacey Chamberlain, Sanita Burgic, Kara Weekley, Béga Murray, S. G. Patel, Faridi Qaium, Andrea N. Lucas, Margaret Fagan, Anne Dufek, Christian F. Meyer, Natalie B. Collins, Christine A. Pratilas, Eva Dombi, Andrea M. Gross, AeRang Kim, John S.A. Chrisinger, Carina Dehner, Brigitte C. Widemann, Angela C. Hirbe, Aadel A. Chaudhuri, Jack F. ShernList of authors in order
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https://doi.org/10.1158/1078-0432.c.7474432Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1158/1078-0432.c.7474432Direct OA link when available
- Concepts
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Peripheral nerve, Peripheral, Medicine, Pathology, DNA, Cancer research, Biology, Internal medicine, Anatomy, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| primary_location.landing_page_url | https://doi.org/10.1158/1078-0432.c.7474432 |
| publication_date | 2024-10-01 |
| publication_year | 2024 |
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