• What is NF1?
  • NF1 in Melanoma
  • NF1 Mutations
  • Clinical Trials

NF1

Neurofibromin 1 (NF1) is a gene that codes for a tumor suppressor protein (Genetics Home Reference 2014). NF1 suppresses the function of the Ras protein, which promotes cell growth and differentiation (Genetics Home Reference 2014; Yap et al. 2014). In cancer, the tumor suppression function of the gene is impaired, leading to conditions favorable for uncontrolled cell growth. NF1 mutations have been observed in multiple cancer types, including myelodysplastic syndromes.

In addition, NF1 syndrome is a germline condition resulting in predisposition to several types of cancer, in addition to other effects (Yap et al. 2014). Cancer types associated with NF1 syndrome include glioma, melanoma, lung cancer, ovarian cancer, breast cancer, colorectal cancer, hematologic malignancies, and other cancers (Yap et al. 2014).​

Related Pathways

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. NF1. My Cancer Genome https://www.padiracinnovation.org/content/disease/melanoma/nf1/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

NF1 (NF1) in Melanoma

NF1 mutations occur in 11.9% of malignant melanomas (COSMIC). Inactivation or loss of NF1 is thought to play a role in melanogenesis (Maertens et al. 2013; Whittaker et al. 2013). Since NF1 is a tumor suppressor gene, mutations to NF1 can result in loss of normal downregulation of the Ras activation of the MAPK and PI3K–Akt–mTOR proliferation and differentiation pathways, among other tumor suppression activities (Gibney and Smalley 2013; Yap et al. 2014).

Contributors: Christine M. Lovly, M.D., Ph.D., Douglas Johnson, M.D., Jeff Sosman, M.D.

Suggested Citation: Lovly, C., D. Johnson, J. Sosman. 2015. NF1 (NF1) in Melanoma. My Cancer Genome https://www.padiracinnovation.org/content/disease/melanoma/nf1/ (Updated June 16).

Last Updated: June 16, 2015

NF1 Mutations in Melanoma

Properties
Location of mutation NF1 gene on 17q11.2
Frequency of NF1 mutations in malignant melanomas 11.9% (COSMIC)
Implications for Targeted Therapeutics
Response to BRAF inhibitors Unknown at this timea
Response to MEK inhibitors Unknown at this timeb
Response to ERK inhibitors Unknown at this time

 

NF1 mutations are inactivating or cause loss of NF1 (Nissan et al. 2014). While many mutations have been described in NF1 in melanoma (Cerami et al. 2012; COSMIC; Gao et al. 2013; Nissan et al. 2014), the overall frequencies of these mutations have not yet been established.

a Melanomas with NF1 mutations have been shown to be resistant to BRAF inhibitors in preclinical studies (Maertens et al. 2013; Whittaker et al. 2013).

b Melanomas with NF1 mutations have been shown to be sensitive to MEK inhibition in preclinical studies (Whittaker et al. 2013).

Contributors: Christine M. Lovly, M.D., Ph.D., Douglas Johnson, M.D., Jeff Sosman, M.D.

Suggested Citation: Lovly, C., D. Johnson, J. Sosman. 2015. NF1 Mutations in Melanoma. My Cancer Genome https://www.padiracinnovation.org/content/disease/melanoma/nf1/325/ (Updated June 16).

Last Updated: June 16, 2015

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