1999
DOI: 10.1126/science.286.5447.2176
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Mouse Tumor Model for Neurofibromatosis Type 1

Abstract: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by increased incidence of benign and malignant tumors of neural crest origin. Mutations that activate the protooncogene ras, such as loss of Nf1, cooperate with inactivating mutations at the p53 tumor suppressor gene during malignant transformation. One hundred percent of mice harboring null Nf1 and p53 alleles in cis synergize to develop soft tissue sarcomas between 3 and 7 months of age. These sarcomas exhibit loss of heterozygosi… Show more

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Cited by 360 publications
(281 citation statements)
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“…Survival as well as tumor incidence was compared with C57BL/6, Cpt1c gt/gt and Nf1 þ / À : p53 þ / À mice (Figure 6a). Similar to previous reports, 19,20 we observed that Nf1 þ / À : p53 þ / À mice developed soft tissue sarcomas of the limbs and abdomen as well as lymphomas at around 3-6 months of age and with a penetrance of over 70%. CPT1C depletion in this murine tumor model highly increases the median survival time from 5-15 months (Po0.0001).…”
Section: Resultssupporting
confidence: 79%
See 1 more Smart Citation
“…Survival as well as tumor incidence was compared with C57BL/6, Cpt1c gt/gt and Nf1 þ / À : p53 þ / À mice (Figure 6a). Similar to previous reports, 19,20 we observed that Nf1 þ / À : p53 þ / À mice developed soft tissue sarcomas of the limbs and abdomen as well as lymphomas at around 3-6 months of age and with a penetrance of over 70%. CPT1C depletion in this murine tumor model highly increases the median survival time from 5-15 months (Po0.0001).…”
Section: Resultssupporting
confidence: 79%
“…To verify this hypothesis, we used the neurofibromatosis type I tumor model. 18,19 Nf1 þ / À : p53 þ / À mice, which are prone to develop soft tissue sarcomas, were crossed with Cpt1c gt/gt mice to generate Nf1 þ / À : p53 þ / À : Cpt1c gt/gt mice in a C57BL/6 background. Survival as well as tumor incidence was compared with C57BL/6, Cpt1c gt/gt and Nf1 þ / À : p53 þ / À mice (Figure 6a).…”
Section: Resultsmentioning
confidence: 99%
“…To test this possibility, mice carrying null mutations of both Nf1 and Trp53 on the same (cis-linked Nf1 þ/À ;Trp53 þ/À mice) and different (trans Nf1 þ/À ;Trp53 þ/À mice) copies of chromosome 11 were created. 88,89 In mice, the most common mechanism of second hit mutation is whole chromosome loss. Consistent with this, 30% of cis-linked Nf1 þ/À ;Trp53 þ/À mice developed MPNSTs by 5 months of age, whereas trans Nf1 þ/À ;Trp53 þ/À mice typically died at 10 months of age with other tumor types characteristic of Trp53 þ/À mice.…”
Section: Currently Available Mouse Models Of Neurofibroma and Mpnst Pmentioning
confidence: 99%
“…There is evidence to support a role of p53 in the formation of MPNST. Mice that are heterozygous for both an NF1 and p53 mutation develop sarcomas [72,73], and human MPNST have been found to have mutation of p53 in addition to NF1 [74]. It is possible that other dominant or recessive oncogenes also contribute towards malignancy in other NF1-associated lesions.…”
Section: Molecular Pathogenesis and Insights Into Treatmentmentioning
confidence: 99%