NDLI: Transgenic Mice Overexpressing Neuregulin-1 Model Neurofibroma-Malignant Peripheral Nerve Sheath Tumor Progression and Implicate Specific Chromosomal Copy Number Variations in Tumorigenesis

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kazmi, Syed J. Byer, Stephanie J. Eckert, Jenell M. Turk, Amy N. Huijbregts, Richard P. H. Brossier, Nicole M. Grizzle, William E. Mikhail, Fady M. Roth, Kevin A. Carroll, Steven L.
Description	Country affiliation: United States Author Affiliation: Kazmi SJ ( Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama 35294-0017, USA.)
Abstract	Patients with neurofibromatosis type 1 (NF1) develop benign plexiform neurofibromas that frequently progress to become malignant peripheral nerve sheath tumors (MPNSTs). A genetically engineered mouse model that accurately models plexiform neurofibroma-MPNST progression in humans would facilitate identification of somatic mutations driving this process. We previously reported that transgenic mice overexpressing the growth factor neuregulin-1 in Schwann cells (P(0)-GGFß3 mice) develop MPNSTs. To determine whether P(0)-GGFß3 mice accurately model human neurofibroma-MPNST progression, cohorts of these animals were monitored through death and were necropsied; 94% developed multiple neurofibromas, with 70% carrying smaller numbers of MPNSTs. Nascent MPNSTs were identified within neurofibromas, suggesting that these sarcomas arise from neurofibromas. Although neurofibromin expression was maintained, P(0)-GGFß3 MPNSTs exhibited Ras hyperactivation, as in human NF1-associated MPNSTs. P(0)-GGFß3 MPNSTs also exhibited abnormalities in the p16(INK4A)-cyclin D/CDK4-Rb and p19(ARF)-Mdm-p53 pathways, analogous to their human counterparts. Array comparative genomic hybridization (CGH) demonstrated reproducible chromosomal alterations in P(0)-GGFß3 MPNST cells (including universal chromosome 11 gains) and focal gains and losses affecting 39 neoplasia-associated genes (including Pten, Tpd52, Myc, Gli1, Xiap, and Bbc3/PUMA). Array comparative genomic hybridization also identified recurrent focal copy number variations affecting genes not previously linked to neurofibroma or MPNST pathogenesis. We conclude that P(0)-GGFß3 mice represent a robust model of neurofibroma-MPNST progression useful for identifying novel genes driving neurofibroma and MPNST pathogenesis.
File Format	HTM / HTML
ISSN	00029440
e-ISSN	15252191
DOI	10.1016/j.ajpath.2012.11.017
Journal	The American Journal of Pathology
Issue Number	3
Volume Number	182
Language	English
Publisher	Elsevier (on behalf of the American Society for Investigative Pathology)
Publisher Date	2013-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Dna Copy Number Variations Research Support, N.i.h., Extramural Neurofibromin 1 Peripheral Nervous System Nerve Sheath Neoplasms Neuregulin-1 Genetics Disease Models, Animal Research Support, U.s. Gov't, Non-p.h.s. Tumor Markers, Biological Signal Transduction Mice, Inbred C57bl Mice, Transgenic Discipline Pathology Metabolism Chromosomes, Mammalian Disease Progression Pathology Animals Base Pairing Cell Cycle Comparative Genomic Hybridization Cell Transformation, Neoplastic Ras Proteins Mice Neurofibroma
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Transgenic Mice Overexpressing Neuregulin-1 Model Neurofibroma-Malignant Peripheral Nerve Sheath Tumor Progression and Implicate Specific Chromosomal Copy Number Variations in Tumorigenesis

Trp53 haploinsufficiency modifies EGFR-driven peripheral nerve sheath tumorigenesis.

Neurofibromin Deficiency Causes Epidermal Growth Factor Receptor Upregulation through the Activation of Ras/ERK/SP1 Signaling Pathway in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheet Tumor

Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report

Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

Abdominal neoplastic manifestations of neurofibromatosis type 1

A giant posterior mediastinal malignant peripheral nerve sheath tumor and benign neurofibroma in body surface: a case report

Statins, bone, and neurofibromatosis type 1

Neurofibromin-deficient fibroblasts fail to form perineurium in vitro.

Transgenic Mice Overexpressing Neuregulin-1 Model Neurofibroma-Malignant Peripheral Nerve Sheath Tumor Progression and Implicate Specific Chromosomal Copy Number Variations in Tumorigenesis

Similar Documents

Transgenic Mice Overexpressing Neuregulin-1 Model Neurofibroma-Malignant Peripheral Nerve Sheath Tumor Progression and Implicate Specific Chromosomal Copy Number Variations in Tumorigenesis

Trp53 haploinsufficiency modifies EGFR-driven peripheral nerve sheath tumorigenesis.

Neurofibromin Deficiency Causes Epidermal Growth Factor Receptor Upregulation through the Activation of Ras/ERK/SP1 Signaling Pathway in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheet Tumor

Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report

Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

Abdominal neoplastic manifestations of neurofibromatosis type 1

A giant posterior mediastinal malignant peripheral nerve sheath tumor and benign neurofibroma in body surface: a case report

Statins, bone, and neurofibromatosis type 1

Neurofibromin-deficient fibroblasts fail to form perineurium in vitro.

Transgenic Mice Overexpressing Neuregulin-1 Model Neurofibroma-Malignant Peripheral Nerve Sheath Tumor Progression and Implicate Specific Chromosomal Copy Number Variations in Tumorigenesis