363 NF1 heterozygosity fosters de novo tumorigenesis but impairs malignant transformation

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder. Patients with NF1 have mono-allelic loss of the tumor suppressor gene NF1 in their germline, which predisposes them to develop a wide array of benign lesions. Intriguingly, recent sequencing efforts revealed that the NF1 gene is frequently mutated in multiple malignant tumors not typically associated with NF1 patients, suggesting that NF1 heterozygosity is refractory to at least some cancer types. In two orthogonal mouse models representing tumors associated with NF1 (neurofibroma and malignant peripheral nerve sheath tumor) and non-NF1-related tumors (papilloma and squamous cell carcinoma), we serendipitously discover that an NF1heterozygosity microenvironment accelerates the formation of benign tumors but impairs further progression to malignancy.

Source: Journal of Investigative Dermatology - April 19, 2019 Category: Dermatology Authors: J. Brosseau, C. Liao, Y. Wang, V. Ramani, T. Vandergriff, M. Lee, A. Patel, K. Ariizumi, L. Le Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research