Mahalingam, "NF1 and Neurofibromin
: Emerging Players in the Genetic Landscape of Desmoplastic Melanoma," Advances in Anatomic Pathology, vol.
The NF1 is a tumor suppressor gene encoding a RAS GTPase-activating protein called neurofibromin
, which is a large multi-domain 2818 amino acid protein.[sup] Hitherto, more than 2000 various causative mutations of NF1 gene associated with NF1 have been recorded in the HGMD database including missense, nonsense, splice-site, and frameshift mutations.
Zhang et al., "Neurofibromin
is a novel regulator of Ras-induced reactive oxygen species production in mice and humans," Free Radical Biology & Medicine, vol.
Injection of adenovirus expressing Cre into mice carrying floxed alleles of Nf1 and Cdkn2a drives high-grade MPNST through localized loss of neurofibromin
, [p16.sup.Ink4a], and [p19.sup.Arf] in the nerve .
(5) in their report on an adult with neurofibromatosis type 1 who developed chronic myeloid leukemia suggest a possible synergistic action between the absence of neurofibromin
and the presence of tyrosine kinase activity of BCR/ABL gene.
 Human genes: NF1, neurofibromin
1; RET, ret protooncogene; VHL, von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase; SDHB, succinate dehydrogenase complex, subunit B, iron sulfur (Ip); SDHD, succinate dehydrogenase complex, subunit D, integral membrane protein.
gene defect has been located on Chromosome 18.
It has recently been shown that neurofibromatosis 1 (NF1) is associated with a defect in the neurofibromin
gene on chromosome 17 and NF2 with a defect in the merlin/ schwannomin gene on chromosome 22.
Regulation of neurofibromin
by post- translational modification.
NF1 is a tumor suppressor that encodes for the neurofibromin
protein, a member of the Ras family.
(1-3) The NF1 gene is on chromosome 17q11.2, which encodes for neurofibromin
Diagnosis of the autosomal dominant syndrome--which results from a neurofibromin
defect and occurs in 1 of 2,000-4,500 individuals--requires the presence of two or more of the following diagnostic criteria: six or more CALMs greater than 0.5 cm in diameter in prepubertal children, or greater than 1.5 cm in those postpubertal; two or more neurofibromas of any type, or one plexiform neurofibroma; axillary and/or inguinal freckling (Crowe's sign); optic glioma; two or more Lisch nodules; a bony lesion (such as sphenoid dysplasia or long bone dysplasia); and a first-degree relative with NF1.