BACKGROUND: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder 
resulting in the growth of a variety of tumours, and is inherited in an 
autosomal dominant pattern. Gastrointestinal stromal tumours (GISTs) are 
mesenchymal tumours that commonly harbour oncogenic mutations in KIT or PDGFRA 
and are thought to arise from the interstitial cells of Cajal (ICC; the 
pacemaker cells of the gut).
AIM: To characterise two patients with NF1 and GISTs.
METHODS: Two patients were genotyped for germline mutations in NF1. GISTs from 
both patients were genotyped for somatic mutations in KIT and PDGFRA. Loss of 
heterozygosity (LOH) of NF1 in one GIST was assessed by genotyping seven 
microsatellite markers spanning 2.39 Mb of the NF1 locus in the tumour and in 
genomic DNA. The known germline mutation in NF1 was confirmed in GIST DNA by 
sequencing. The copy number of the mutated NF1 allele was determined by 
multiplex ligand-dependent probe amplification.
RESULTS: GISTs from both patients were of wild type for mutations in KIT and 
PDGFRA. In the GIST with adequate DNA, all seven markers were informative and 
showed LOH at the NF1 locus; sequencing of NF1 from that GIST showed no 
wild-type sequence, suggesting that it was lost in the tumour. Multiplex 
ligand-dependent probe amplification analysis showed that two copies of all NF1 
exons were present.
CONCLUSIONS: This is the first evidence of mitotic recombination resulting in a 
reduction to homozygosity of a germline NF1 mutation in an NF1-associated GIST. 
We hypothesise that the LOH of NF1 and lack of KIT and PDGFRA mutations are 
evidence of an alternative pathogenesis in NF1-associated GISTs.