Chetan Bettegowda1, Meena Upadhayaya1, D Gareth Evans1, AeRang Kim1, Dimitrios Mathios1, Clemens O Hanemann2. 1. From 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. 2. From 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. Oliver.Hanemann@plymouth.ac.uk.
Abstract
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.
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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