Optic pathway gliomas in neurofibromatosis-1: Controversies and recommendations
Division of General Academic Pediatrics, Department of Pediatrics, Children's Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.Annals of Neurology (Impact Factor: 9.98). 03/2007; 61(3):189-98. DOI: 10.1002/ana.21107
Optic pathway glioma (OPG), seen in 15% to 20% of individuals with neurofibromatosis type 1 (NF1), account for significant morbidity in young children with NF1. Overwhelmingly a tumor of children younger than 7 years, OPG may present in individuals with NF1 at any age. Although many OPG may remain indolent and never cause signs or symptoms, others lead to vision loss, proptosis, or precocious puberty. Because the natural history and treatment of NF1-associated OPG is different from that of sporadic OPG in individuals without NF1, a task force composed of basic scientists and clinical researchers was assembled in 1997 to propose a set of guidelines for the diagnosis and management of NF1-associated OPG. This new review highlights advances in our understanding of the pathophysiology and clinical behavior of these tumors made over the last 10 years. Controversies in both the diagnosis and management of these tumors are examined. Finally, specific evidence-based recommendations are proposed for clinicians caring for children with NF1.
- "Bilateral OPGs are considered pathognomonic for NF1 and are one of the diagnosis criteria of NF1. The co-occurrence of NF1 in an OPG patient is considered a good prognostic factor (Listernick, Ferner et al. 2007; McClatchey 2007). In a recent series comparing NF1 OPG to sporadic gliomas, children with NF1 had a significantly better clinical picture at diagnosis, with less increase in intracranial pressure, less decrease in visual acuity, and fewer abnormalities of fundus of the eye. "
Article: Optic Pathway Gliomas[Show abstract] [Hide abstract]
ABSTRACT: Optic pathway gliomas (OPGs) are among the most challenging neoplasms in modern pediatric neuro-oncology. Recent technological advances in imaging, surgery, and chemotherapy may lead to better understanding of the pathophysiology and better clinical results. This chapter reviews these advances and the current treatment paradigms.Advances and technical standards in neurosurgery 01/2015; 42:123-46. DOI:10.1007/978-3-319-09066-5_7
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- "While further experimentation will be required, it is possible that different stem cell niches are uniquely affected by both the specific cancer-associated genetic change (Nf1 loss vs. combined Nf1, p53, and Pten inactivation) and the developmental age of the animal (young vs. adult mice). These determinants may be particularly relevant to the distinct spatial and temporal pattern of gliomagenesis in patients with NF1 (optic pathway and BS gliomas arising in children <10 yr of age) (Listernick et al. 2007). In summary, we provide a mechanistic explanation for the differential response of spatially distinct populations of brain NSCs to neurofibromin loss. "
ABSTRACT: Recent studies have shown that neuroglial progenitor/stem cells (NSCs) from different brain regions exhibit varying capacities for self-renewal and differentiation. In this study, we used neurofibromatosis-1 (NF1) as a model system to elucidate a novel molecular mechanism underlying brain region-specific NSC functional heterogeneity. We demonstrate that Nf1 loss leads to increased NSC proliferation and gliogenesis in the brainstem, but not in the cortex. Using Nf1 genetically engineered mice and derivative NSC neurosphere cultures, we show that this brain region-specific increase in NSC proliferation and gliogenesis results from selective Akt hyperactivation. The molecular basis for the increased brainstem-specific Akt activation in brainstem NSCs is the consequence of differential rictor expression, leading to region-specific mammalian target of rapamycin (mTOR)/rictor-mediated Akt phosphorylation and Akt-regulated p27 phosphorylation. Collectively, these findings establish mTOR/rictor-mediated Akt activation as a key driver of NSC proliferation and gliogenesis, and identify a unique mechanism for conferring brain region-specific responses to cancer-causing genetic changes.Genes & development 09/2010; 24(20):2317-29. DOI:10.1101/gad.1957110 · 10.80 Impact Factor
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- "Approximately 15–20% of NF1 patients develop low-grade astrocytomas with homozygous inactivation of the neurofibromin (NF1) gene in the neoplastic cells (Gutmann et al., 2000; Kluwe et al., 2001; Listernick et al., 1997). While loss of the second NF1 allele is likely to be a random event, NF1-associated gliomas predominantly occur in optic nerve and chiasm of young children (Listernick et al., 2007). This unique pattern of tumorigenesis, referred to as optic pathway glioma (OPG), suggests the existence of a secondary mechanism that specifies the timing and location of tumor formation. "
ABSTRACT: Tumorigenesis requires interactions between tumor progenitors and their microenvironment. We found that low cAMP levels were sufficient for tumorigenesis in a mouse model of Neurofibromatosis-1 (NF1)-associated optic pathway glioma (OPG). We hypothesized that the distinct pattern of glioma in NF1 reflected spatiotemporal differences in CXCL12 effects on cAMP levels. Thus, we sought to alter the pattern of gliomagenesis through manipulation of CXCL12-CXCR4 pathway activation in Nf1 OPG mice. Forced CXCL12 expression induced glioma at a low frequency. Further, treatment of Nf1 OPG mice with AMD3100, a CXCR4 antagonist, did not attenuate glioma growth. Thus, it appears, CXCL12 alone cannot promote gliomagenesis in NF1 mice.Journal of neuroimmunology 07/2010; 224(1-2):108-13. DOI:10.1016/j.jneuroim.2010.05.002 · 2.47 Impact Factor
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