@article{3011971ef6fc4e39bcf3930702ece520,
title = "Spatiotemporal loss of NF1 in schwann cell lineage leads to different types of cutaneous neurofibroma susceptible to modification by the hippo pathway",
abstract = "Neurofibromatosis type 1 (NF1) is a cancer predisposition disorder that results from inactivation of the tumor suppressor neurofibromin, a negative regulator of RAS signaling. Patients with NF1 present with a wide range of clinical manifestations, and the tumor with highest prevalence is cutaneous neurofibroma (cNF). Most patients harboring cNF suffer greatly from the burden of those tumors, which have no effective medical treatment. Ironically, none of the numerous NF1 mouse models developed so far recapitulate cNF. Here, we discovered that HOXB7 serves as a lineage marker to trace the developmental origin of cNF neoplastic cells. Ablating Nf1 in the HOXB7 lineage faithfully recapitulates both human cutaneous and plexiform neurofibroma. In addition, we discovered that modulation of the Hippo pathway acts as a “modifier” for neurofibroma tumorigenesis. This mouse model opens the doors for deciphering the evolution of cNF to identify effective therapies, where none exist today. SIGNIFICANCE: This study provides insights into the developmental origin of cNF, the most common tumor in NF1, and generates the first mouse model that faithfully recapitulates both human cutaneous and plexiform neurofibroma. The study also demonstrates that the Hippo pathway can modify neurofibromagenesis, suggesting that dampening the Hippo pathway could be an attractive therapeutic target.",
author = "Zhiguo Chen and Juan Mo and Brosseau, {Jean Philippe} and Tracey Shipman and Yong Wang and Liao, {Chung Ping} and Cooper, {Jonathan M.} and Allaway, {Robert J.} and Gosline, {Sara J.C.} and Justin Guinney and Carroll, {Thomas J.} and Le, {Lu Q.}",
note = "Funding Information: We thank all members of the Le lab for helpful suggestions and discussions. J.-P. Brosseau and C.-P. Liao are recipients of the Young Investigator Award from the Children{\textquoteright}s Tumor Foundation. C.-P. Liao also received a Career Development Award from the Dermatology Foundation. J.M. Cooper is funded by the Dermatology Research Training Program T32 Grant T32AR065969. L.Q. Le holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and the Thomas L. Shields, M.D. Professorship in Dermatology. This work was supported by funding from the NCI of the NIH grant number R01 CA166593, the U.S. Department of Defense grant number W81XWH-17-1-0148, the Giorgio Foundation, the Neurofibromatosis Therapeutic Acceleration Program, and the NF1 Research Consortium Fund to L.Q. Le. Publisher Copyright: {\textcopyright} 2019 American Association for Cancer Research.",
year = "2019",
month = jan,
doi = "10.1158/2159-8290.CD-18-0151",
language = "English",
volume = "9",
pages = "114--129",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "1",
}