An Update on Neurofibromatosis Type 1-Associated Gliomas

Lobbous, Mina; Bernstock, Joshua D.; Coffee, Elizabeth; Friedman, Gregory K.; Metrock, Laura K.; Chagoya, Gustavo; Elsayed, Galal; Nakano, ﻿Ichiro; Hackney, James R.; Korf, Bruce R.; Nabors, Louis B.

doi:10.3390/cancers12010114

Cited by 68 publications

(52 citation statements)

References 112 publications

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“…The most common central nervous system tumours in NF1 are gliomas [reviewed by 73]. Gliomas usually affect children with NF1; the mean age at diagnosis is 4.5 years.…”

Section: Gliomasmentioning

confidence: 99%

Clinical characterization of children and adolescents with NF1 microdeletions

et al. 2020

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Purpose An estimated 5–11% of patients with neurofibromatosis type 1 (NF1) harbour NF1 microdeletions encompassing the NF1 gene and its flanking regions. The purpose of this study was to evaluate the clinical phenotype in children and adolescents with NF1 microdeletions. Methods We retrospectively analysed 30 children and adolescents with NF1 microdeletions pertaining to externally visible neurofibromas. The internal tumour load was determined by volumetry of whole-body magnetic resonance imaging (MRI) in 20 children and adolescents with NF1 microdeletions. Furthermore, the prevalence of global developmental delay, autism spectrum disorder and attention deficit hyperactivity disorder (ADHD) were evaluated. Results Children and adolescents with NF1 microdeletions had significantly more often cutaneous, subcutaneous and externally visible plexiform neurofibromas than age-matched patients with intragenic NF1 mutations. Internal neurofibromas were detected in all 20 children and adolescents with NF1 microdeletions analysed by whole-body MRI. By contrast, only 17 (61%) of 28 age-matched NF1 patients without microdeletions had internal tumours. The total internal tumour load was significantly higher in NF1 microdeletion patients than in NF1 patients without microdeletions. Global developmental delay was observed in 28 (93%) of 30 children with NF1 microdeletions investigated. The mean full-scale intelligence quotient in our patient group was 77.7 which is significantly lower than that of patients with intragenic NF1 mutations. ADHD was diagnosed in 15 (88%) of 17 children and adolescents with NF1 microdeletion. Furthermore, 17 (71%) of the 24 patients investigated had T-scores ≥ 60 up to 75, indicative of mild to moderate autistic symptoms, which are consequently significantly more frequent in patients with NF1 microdeletions than in the general NF1 population. Also, the mean total T-score was significantly higher in patients with NF1 microdeletions than in the general NF1 population. Conclusion Our findings indicate that already at a very young age, NF1 microdeletions patients frequently exhibit a severe disease manifestation which requires specialized long-term clinical care.

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“…The most common central nervous system tumours in NF1 are gliomas [reviewed by 73]. Gliomas usually affect children with NF1; the mean age at diagnosis is 4.5 years.…”

Section: Gliomasmentioning

confidence: 99%

Clinical characterization of children and adolescents with NF1 microdeletions

et al. 2020

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“…Other NF1-associated tumours are the optic pathway gliomas (OPGs), occurring in approximately 15% of NF1 individuals. They are most commonly found in young children (less than 7 years of age) and rarely in adolescents or adults [ 283 , 324 , 325 , 326 , 327 ]. These tumours may involve the optic nerve, chiasm and/or hypothalamus.…”

Section: Neurofibromatosismentioning

confidence: 99%

“…Therefore, neurofibromin—acting as a negative modulator of the Ras signalling—exerts a tumour suppressor activity. Figure was redrawn from Lobbous et al [ 283 ].…”

Section: Figurementioning

confidence: 99%

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Riccardi

Perrone

Napolitano

et al. 2020

Cancers

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Vitamin D is a fat-soluble steroid hormone playing a pivotal role in calcium and phosphate homeostasis as well as in bone health. Vitamin D levels are not exclusively dependent on food intake. Indeed, the endogenous production—occurring in the skin and dependent on sun exposure—contributes to the majority amount of vitamin D present in the body. Since vitamin D receptors (VDRs) are ubiquitous and drive the expression of hundreds of genes, the interest in vitamin D has tremendously grown and its role in different diseases has been extensively studied. Several investigations indicated that vitamin D action extends far beyond bone health and calcium metabolism, showing broad effects on a variety of critical illnesses, including cancer, infections, cardiovascular and autoimmune diseases. Epidemiological studies indicated that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumour predisposition syndrome causing significant pain and morbidity, for which limited treatment options are available. In this context, vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, alone or combined with other therapeutic agents. Here we provide an overview of vitamin D, its characteristic nutritional properties relevant for health benefits and its role in NF1 disorder. We focus on preclinical and clinical studies that demonstrated the clinical correlation between vitamin D status and NF1 disease, thus providing important insights into disease pathogenesis and new opportunities for targeted therapy.

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“…It is well-known that neurofibromin has an important function in cancer development and progression. Bi-allelic loss of neurofibromin confers a growth advantage in astrocytes in vitro and is required for tumor formation (30,31).…”

Section: Discussionmentioning

confidence: 99%

Pediatric Diffuse Midline Gliomas H3 K27M-Mutant and Non-Histone Mutant Midline High-Grade Gliomas in Neurofibromatosis Type 1 in Comparison With Non-Syndromic Children: A Single-Center Pilot Study

et al. 2020

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Conclusions: Cerebral HGGs arising in midline structures rarely occur in pediatric patients with NF1 and present with extremely poor prognosis, worse than HGGs developing in non-NF1 patients, independent of the presence or absence of H3 K27M mutation. Imaging features of aggressive biological activity on advanced MRI or amino-acid PET imaging suggest prompt neuropathological and molecular investigations.

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An Update on Neurofibromatosis Type 1-Associated Gliomas

Cited by 68 publications

References 112 publications

Clinical characterization of children and adolescents with NF1 microdeletions

Clinical characterization of children and adolescents with NF1 microdeletions

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Pediatric Diffuse Midline Gliomas H3 K27M-Mutant and Non-Histone Mutant Midline High-Grade Gliomas in Neurofibromatosis Type 1 in Comparison With Non-Syndromic Children: A Single-Center Pilot Study

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