NF1 heterozygosity fosters de novo tumorigenesis but impairs malignant transformation

Jean Philippe Brosseau, Chung Ping Liao, Yong Wang, Vijay Ramani, Travis Vandergriff, Michelle Lee, Amisha Patel, Kiyoshi Ariizumi, Lu Q. Le

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

Neurofibromatosis type 1 (NF1) is an autosomal genetic disorder. Patients with NF1 are associated with 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 NF1- and non-NF1-related tumors, we discover that an Nf1+/− microenvironment accelerates the formation of benign tumors but impairs further progression to malignancy. Analysis of benign and malignant tumors commonly associated with NF1 patients, as well as those with high NF1 gene mutation frequency, reveals an antagonistic role for NF1 heterozygosity in tumor initiation and malignant transformation and helps to reconciliate the role of the NF1 gene in both NF1 and non-NF1 patient contexts.
原文英語
文章編號5014
期刊Nature Communications
9
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2018
對外發佈Yes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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