Other NF1 Research

Predictive value of café-au-lait macules for the diagnosis of NF1

Café-au-lait macule

Children with NF1 often come to medical attention when birthmarks called café-au-lait macules are found on their skin; however, it is not known whether the presence of these birthmarks can accurately predict who will develop NF1 or what features of NF1 they will have.

Studies are ongoing with Dr. Susan Mallory and her colleagues in Dermatology to define the utility of café-au-lait macule shape and number in determining who will eventually be diagnosed with NF1. These investigations are designed to better characterize the dermatologic (skin) features associated with NF1 and understand their clinical importance in the management of children suspected of having this condition.

Additional reading

Kumar MG, Emnett RJ, Bayliss SJ, Gutmann DH. Glomus tumors in individuals with neurofibromatosis type 1. J Am Acad Dermatol. 71: 44-8, 2014.

Nunley KS, Gao F, Albers AC, Bayliss SJ, Gutmann DH. Predictive value of café-au-lait macules at initial consultation in the diagnosis of neurofibromatosis type 1. Arch. Dermat. 145: 883-7, 2009.

Developing small-animal models to promote personalized medicine

A new initiative is focused on developing mouse models of brain tumors and attention deficits that incorporate the specific NF1 genetic mutations observed in people with NF1. These unique strains will be employed to develop more individualized treatments for children and adults with NF1-associated clinical problems.

Additional reading

Gutmann DH. Eliminating barriers to precision medicine: Learning from neurofibromatosis type 1. Neurology. (in press)

Improving therapies for NF1 malignant peripheral nerve sheath tumors (MPNST)

MPNSTOne area of study is focused on identifying the genetic changes that predict malignant transformation and spread (metastasis) or MPNSTs using advanced genomic sequencing strategies. A second area of investigation aims to develop better small-animal models of MPNST development and metastasis to provide a platform to find better treatment strategies for these deadly cancers.

Additional reading

Hirbe AC, Pekmezci M, Dahiya S, Apicelli AJ, Van Tine BA, Perry A, Gutmann DH. BRAFV600E mutation in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors. Neuro Oncol. 16: 466-7, 2014.

Yu J, Deshmukh H, Payton JE, Durham C, Scheithauer BW, Tihan T, Prayson RA, Guha A, Bridge JA, Ferner RE, Lindberg GM, Gutmann RJ, Emnett RJ, Salavaggione L, Gutmann DH, Nagarajan R, Watson MA, Perry A. Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Clin Cancer Res. 17: 1924-34, 2011.

Bhola P, Banerjee S, Mukherjee J, Balasubramanium A, Arun V, Karim Z, Burrell K, Croul S, Gutmann DH, Guha A. Preclinical in vivo evaluation of rapamycin in human malignant peripheral nerve sheath explant xenograft. Int. J Cancer. 126: 563-71, 2010.

Miller SJ, Rangwala F, Williams J, Ackerman P, Kong S, Jegga AG, Kaiser S, Aronow BJ, Frahm S, Luwe L, Mautner V, Updahyaya M, Muir D, Wallace M, Hagen J, Quelle DE, Watson MA, Perry A, Gutmann DH, Ratner N. Large-scale molecular comparison of human schwann cells to malignant nerve sheath tumor cell lines and tissues. Cancer Res. 66: 2584-91, 2006.