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NF1

From www.haematologyetc.co.uk



Gene affected:
NF1: Neurofibromin 1 gene


Clinical significance
NF1 is a frequently mutated gene in myeloid disorders. NF1 acts to supress RAS activity, therefore the outcome of NF1 mutation is to cause activation of RAS pathways. Germline mutation leads to neurofibromatosis 1 with recognised increased incidence of leukaemia. Acquired somatic mutations are seen across a range of myeloid disorders and may carry adverse prognostic effect.



Function of gene

NF1 is a negative regulator of the activity of the RAS family of signaling proteins, loss of function of NF1 is believed therefore to be equivalent activating mutations affecting RAS genes.


Cytogenetic Mapping

Maps to 17q11


NGS panel gene coverage

Whole gene


Occurrence:


Germline changes
Heterozygotic mutation of the neurofibromin 1 gene (NF1) underlies the inherited disorder neurofibromatosis type 1. Affected individuals have higher risk of developing juvenile myelomonocytic leukemia and/or acute myeloid leukemia (AML).
AML (3-7%)
All age groups including de novo presentations, may have an adverse prognostic impact in patients treated with standard chemotherapy
CMML (4%)
May have an adverse prognostic impact.
MDS or MPD (1-2%)
Impact unclear


Links


GeneWiki link:
Gene Wiki entry for NF1


References
1. NF1 in AML
2 NF1 General myeloid incidence
3. Abstract only, describes frequencies and possible prognostic implications