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Volume 11
Issue 5
10.3390/genes11050499
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Article

Unmasking Intra-Tumoral Heterogeneity and Clonal Evolution in NF1-MPNST

by
Chang-In Moon
1,†,
William Tompkins
2,†,
Yuxi Wang
1,
Abigail Godec
3,
Xiaochun Zhang
1,
Patrik Pipkorn
4,5,
Christopher A. Miller
5,6,
Carina Dehner
7,
Sonika Dahiya
5,7 and
Angela C. Hirbe
1,5,*
1
Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
2
Washington University School of Medicine, St. Louis, MO 63110, USA
3
College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
4
Department of Otolaryngology, Division of Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
5
Siteman Cancer Center, St. Louis, MO 63110, USA
6
McDonnell Genome Institute, Division of Oncology—Stem Cell Biology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
7
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Genes 2020, 11(5), 499; https://doi.org/10.3390/genes11050499
Received: 6 March 2020 / Revised: 19 April 2020 / Accepted: 30 April 2020 / Published: 1 May 2020
(This article belongs to the Special Issue Genomics and Models of Nerve Sheath Tumors)
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Abstract

Sarcomas are highly aggressive cancers that have a high propensity for metastasis, fail to respond to conventional therapies, and carry a poor 5-year survival rate. This is particularly true for patients with neurofibromatosis type 1 (NF1), in which 8%–13% of affected individuals will develop a malignant peripheral nerve sheath tumor (MPNST). Despite continued research, no effective therapies have emerged from recent clinical trials based on preclinical work. One explanation for these failures could be the lack of attention to intra-tumoral heterogeneity. Prior studies have relied on a single sample from these tumors, which may not be representative of all subclones present within the tumor. In the current study, samples were taken from three distinct areas within a single tumor from a patient with an NF1-MPNST. Whole exome sequencing, RNA sequencing, and copy number analysis were performed on each sample. A blood sample was obtained as a germline DNA control. Distinct mutational signatures were identified in different areas of the tumor as well as significant differences in gene expression among the spatially distinct areas, leading to an understanding of the clonal evolution within this patient. These data suggest that multi-regional sampling may be important for driver gene identification and biomarker development in the future. View Full-Text
Keywords: NF1; MPNST; genomics; heterogeneity NF1; MPNST; genomics; heterogeneity
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MDPI and ACS Style

Moon, C.-I.; Tompkins, W.; Wang, Y.; Godec, A.; Zhang, X.; Pipkorn, P.; Miller, C.A.; Dehner, C.; Dahiya, S.; Hirbe, A.C. Unmasking Intra-Tumoral Heterogeneity and Clonal Evolution in NF1-MPNST. Genes 2020, 11, 499. https://doi.org/10.3390/genes11050499

AMA Style

Moon C-I, Tompkins W, Wang Y, Godec A, Zhang X, Pipkorn P, Miller CA, Dehner C, Dahiya S, Hirbe AC. Unmasking Intra-Tumoral Heterogeneity and Clonal Evolution in NF1-MPNST. Genes. 2020; 11(5):499. https://doi.org/10.3390/genes11050499

Chicago/Turabian Style

Moon, Chang-In; Tompkins, William; Wang, Yuxi; Godec, Abigail; Zhang, Xiaochun; Pipkorn, Patrik; Miller, Christopher A.; Dehner, Carina; Dahiya, Sonika; Hirbe, Angela C. 2020. "Unmasking Intra-Tumoral Heterogeneity and Clonal Evolution in NF1-MPNST" Genes 11, no. 5: 499. https://doi.org/10.3390/genes11050499

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