NF1 heterozygosity fosters de novo tumorigenesis but impairs malignant transformation

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number5014
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Neurofibromatosis 1
Tumors
Carcinogenesis
tumors
genes
Genes
Neurofibromatosis 1 Genes
tumor suppressor genes
sequencing
refractories
Neoplasms
mutations
progressions
lesions
mice
Refractory materials
cancer
disorders
Inborn Genetic Diseases
Loss of Heterozygosity

ASJC Scopus subject areas

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

Cite this

NF1 heterozygosity fosters de novo tumorigenesis but impairs malignant transformation. / Brosseau, Jean Philippe; Liao Ph.D., Chung Ping; Wang, Yong; Ramani, Vijay; Vandergriff, Travis W; Lee, Michelle; Patel, Amisha; Ariizumi, Kiyoshi; Le, Lu Q.

In: Nature Communications, Vol. 9, No. 1, 5014, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Liao Ph.D., Chung Ping

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AU - Ramani, Vijay

AU - Vandergriff, Travis W

AU - Lee, Michelle

AU - Patel, Amisha

AU - Ariizumi, Kiyoshi

AU - Le, Lu Q

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