The NF1 gene revisited – from bench to bedside
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Yoon-Sim Yap1,2, John R. McPherson3, Choon-Kiat Ong4,5, Steven G. Rozen3, Bin-Tean Teh4,5,6, Ann S. G. Lee7,8,9 and David F. Callen10
1 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
2 Faculty of Health Sciences, School of Medicine, University of Adelaide, Australia
3 Centre for Computational Biology, Cancer and Stem Cell Biology Program, Duke-National University of Singapore Graduate Medical School, Singapore
4 Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore
5 Division of Cancer and Stem Cell Biology, Duke–National University of Singapore Graduate Medical School, Singapore
6 Cancer Science Institute of Singapore, National University of Singapore, Singapore
7 Laboratory of Molecular Oncology, Division of Medical Sciences, National Cancer Centre Singapore, Singapore
8 Office of Clinical & Academic Faculty Affairs, Duke-National University of Singapore Graduate Medical School, Singapore
9 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
10 Cancer Therapeutics Laboratory, Centre for Personalised Cancer Medicine, University of Adelaide, Australia
Yoon-Sim Yap, email:
Keywords: neurofibromatosis type 1, NF1, neurofibromin, cancer
Received: May 15, 2014 Accepted: July 7, 2014 Published: July 9, 2014
Neurofibromatosis type 1 (NF1) is a relatively common tumour predisposition syndrome related to germline aberrations of NF1, a tumour suppressor gene. The gene product neurofibromin is a negative regulator of the Ras cellular proliferation pathway, and also exerts tumour suppression via other mechanisms.
Recent next-generation sequencing projects have revealed somatic NF1 aberrations in various sporadic tumours. NF1 plays a critical role in a wide range of tumours. NF1 alterations appear to be associated with resistance to therapy and adverse outcomes in several tumour types.
Identification of a patient’s germline or somatic NF1 aberrations can be challenging, as NF1 is one of the largest human genes, with a myriad of possible mutations. Epigenetic factors may also contribute to inadequate levels of neurofibromin in cancer cells.
Clinical trials of NF1-based therapeutic approaches are currently limited. Preclinical studies on neurofibromin-deficient malignancies have mainly been on malignant peripheral nerve sheath tumour cell lines or xenografts derived from NF1 patients. However, the emerging recognition of the role of NF1 in sporadic cancers may lead to the development of NF1-based treatments for other tumour types. Improved understanding of the implications of NF1 aberrations is critical for the development of novel therapeutic strategies.
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