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Gene Alterations Replicate Neurofibromatosis in Mice

-- A. Agrawal, PhD

Thursday, October 29, 2009

THURSDAY, Oct. 29 (HealthDay News) -- Mice containing alterations in two genes involved in cellular signaling are a good model for neurofibromatosis (NF) and its transformation into malignant sarcomas, according to a study published online Oct. 21 in the Proceedings of the National Academy of Sciences.

Noting that patients lacking the NF1 gene have a 10 percent lifetime risk of developing malignant peripheral nerve sheath tumors (MPNSTs), Caroline Gregorian, Ph.D., from the University of California in Los Angeles, and colleagues genetically engineered mice with conditional modifications in various cellular signaling pathways implicated in malignant transformation.

The researchers found that only activatable K-ras combined with deletion of one copy of the PTEN gene led to the development of NF lesions and MPNSTs in all mice. Further investigation showed that all mouse MPNSTs and most human NF1-associated MPNSTs had a loss or decrease in PTEN expression. Noninvasive in vivo positron emission tomography-computed tomography imaging using radiolabeled 2-fluoro-2-deoxy-D-glucose could also distinguish between benign and malignant tumors.

"Here, we describe a mouse model for NF and MPNST, which recapitulates the essential clinical features observed in human NF1 and NF-associated MPNSTs," Gregorian and colleagues conclude. "Our study demonstrates the importance of PTEN loss in the NF to MPNST transformation."

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Specialties Cardiology
Diabetes & Endocrinology
Internal Medicine
Family Practice

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