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Genetic Cause for Neurofibromas Discovered

While virtually all adults with Neurofibromatosis type 1 (NF1) develop benign tumors associated with nerves, called neurofibromas, these tumors can also arise in people without NF1 (termed sporadic neurofibromas). In individuals with NF1, neurofibromas are caused by mutations in the NF1 gene; however, the genetic cause for sporadic tumors was previously unknown.

Corina Anastasaki, PhD, a senior research scientist in the laboratory of Dr. David Gutmann, recently found mutations in a gene that likely are responsible for the development of neurofibromas in some individuals without NF1. Using advanced sequencing methods, she discovered mutations in a gene, called KIR2DL5, previously implicated in immune system function, leading to loss of KIR2DL5 expression. Dr. Anastasaki, working with Sonika Dahiya, MD, a neuropathologist at the Washington University School of Medicine, then studied a large independent series of sporadic neurofibromas, and found loss of KIR2DL5 expression in approximately one-third of tumors examined.

To demonstrate that KIR2DL5 was the likely reason for the formation of sporadic neurofibromas, she expressed the mutated KIR2DL5 gene in normal human Schwann cells. Dr. Anastasaki found that mutant KIR2DL5 expression or KIR2DL5 loss increased the growth of Schwann cells, and controlled Schwann cell growth in a manner similar to the NF1 protein, suggesting that treatments that work for NF1-neurofibromas might also be effective for their sporadic counterparts.

Future studies are planned to determine whether this gene can cause neurofibromas in experimental model systems.


Anastasaki C, Dahiya S, Gutmann DH. KIR2DL5 mutation and loss underlies sporadic dermal neurofibroma pathogenesis and growth. Oncotarget. 2017 May 10. doi: 10.18632/oncotarget.17736. PMID: 28548933.