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Genotype-Phenotype Correlations in Neurofibromatosis and Their Potential Clinical Use
Chetan Bettegowda1, Meena Upadhayaya1, D Gareth Evans1
1From Johns Hopkins University School of Medicine (C.B., D.M.), Baltimore, MD; Division Cancer and Genetics (M.U.), Cardiff University; Genomic Medicine (D.G.E.), University of Manchester, UK; Center for Cancer and Blood Disorders (A.K.), Children's National Hospital, Washington, DC; and Faculty of Health, Medicine, Dentistry and Health Sciences (C.O.H.), Institute of Translational and Stratified Medicine, University of Plymouth, UK.
Objective:
Because clinically validated biomarkers for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2) have not been identified, we aimed to determine whether genotype-phenotype correlations are useful in clinical trials in NF1 and NF2.
Methods:
The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Biomarker Group first performed a systematic literature search and reviewed existing data on genetic biomarkers in NF1 and NF2 and in in malignant peripheral nerve sheath tumors. The group then met during a series of consensus meetings to develop a joint report.
Results:
We found that in NF2, the genetic severity score is clearly of potential clinical use. In NF1, despite over 3,000 constitutional variants having been described in the NF1 gene, only 4 actionable genotype-phenotype correlations exist. The diagnosis and treatment decision of these tumors should ideally include histopathology and compilation of some of the genetic markers.
Conclusion:
We summarized emerging clinical use of genotype-phenotype correlations in neurofibromatosis.
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