Posts Categorized: Part 04: CANCER



Recurrent mutations in NF1 and RASopathy genes melanomas

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A whole-exome sequencing (WES) study on 213 melanomas found that NF1, encoding a negative regulator of RAS mutated in Neurofibromatosis type 1, is the third most frequently mutated gene in melanoma, after BRAF and NRAS. Inactivating NF1 mutations were present in 46% of melanomas expressing wild-type BRAF and RAS, occurred in older patients and showed a distinct pattern […]



Risk of tumors in Bohring-Opitz Syndrome

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Bohring-Opitz Syndrome (BOS, MIM 612990) is a rare condition characterized by dysmorphic features, failure to thrive, severe intellectual disability,  nevus flammeus and myopia. It can be caused by heterozygous mutations in ASXL1, a gene involved in the regulation of Hox genes. Russel et al. (AJMG, 2015, Apr 29. doi: 10.1002/ajmg.a.37131. [Epub ahead of print]) just published clinical management […]



Recombinant alkaline phosphatase improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1

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Neurofibromatosis type-1 (NF1) can present with focal skeletal dysplasias that remain extremely difficult to treat. Elefteriou and colleagues report that ablation of Nf1 in bone-forming cells results in accumulation of pyrophosphate (PPi), a strong inhibitor of hydroxyapatite formation, and that a chronic extracellular signal–regulated kinase (ERK)-dependent increase in expression of genes promoting PPi synthesis and extracellular transport, namely Enpp1 […]



Novel therapeutic targets for malignant peripheral nerve sheath tumors

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A recent paper in the Journal of Clinical Investigation identified targets for therapy of malignant peripheral nerve sheath tumors (MPNST) in patients with Neurofibromatosis type 1 (NF1). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras/Raf/MEK/ERK signaling. PD0325901, a highly selective pharmacological inhibitor of MEK, reduced aberrantly […]



IDH1 mutation in gliomas

Posted by & filed under Part 04: CANCER, Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

Certain gliomas have somatic mutation in cytosolic isocitrate dehydrogenase 1. Dang et al. have shown that these mutations confer the enzyme the new ability to transform alpha-ketoglutarate in 2-hydroxyglutarate. This metabolite might be oncogenic, although this is not proven yet. Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009;462:739-744 […]