Analysis of cell cycle regulators: p16INK4A, pRb, and CDK4 in low- and high-grade meningiomas

Tse, Jenny; Ng, Ho Keung; Lo, Kwok Wai; Chong, Edith Y.Y.; Lam, Paula Yeng Po; Ng, Enders K. O.; Poon, Wai Sang; Huang, Dolly P.

doi:10.1016/s0046-8177(98)90246-5

Cited by 33 publications

(19 citation statements)

References 19 publications

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“…These tumor types belong to the typical tumor spectrum of heterozygous p53 mutant mice (Donehower et al 1992). Genetic studies have suggested that inactivation of the retinoblastoma and p53 tumor suppressor genes are uncommon in meningiomas (Pykett et al 1997;Tse et al 1998). Our results suggest that in mice, as in humans, p53 gene inactivation is not a critical event for meningioma development.…”

Section: Meningioma Development In Nf2 Mutant Mice Genes and Developmenmentioning

confidence: 46%

“…Our results suggest that in mice, as in humans, p53 gene inactivation is not a critical event for meningioma development. An additional event thought to be associated with malignant progression in meningiomas is loss of the p16 INK4A tumor suppressor (Tse et al 1998). The availability of meningioma-prone Nf2 conditional mutant mice will greatly facilitate the elucidation of additional genetic factors that influence meningioma development and progression.…”

Section: Meningioma Development In Nf2 Mutant Mice Genes and Developmenmentioning

confidence: 99%

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Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse

Kalamaridès¹,

Niwa‐Kawakita²,

Leblois³

et al. 2002

Genes Dev.

211

128

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Biallelic NF2 gene inactivation is common in sporadic and in neurofibromatosis type 2 (NF2)-related meningiomas. We show that, beginning at four months of age, thirty percent of mice with arachnoidal cell Cre-mediated excision of Nf2 exon 2 developed a range of meningioma subtypes histologically similar to the human tumors. Additional hemizygosity for p53 did not modify meningioma frequency or progression suggesting that Nf2 and p53 mutations do not synergize in meningeal tumorigenesis. This first mouse model initiated with a genetic lesion found in human meningiomas provides a powerful tool for investigating tumor progression and for the preclinical evaluation of therapeutic interventions.

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Section: Meningioma Development In Nf2 Mutant Mice Genes and Developmenmentioning

confidence: 46%

Section: Meningioma Development In Nf2 Mutant Mice Genes and Developmenmentioning

confidence: 99%

Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse

Kalamaridès¹,

Niwa‐Kawakita²,

Leblois³

et al. 2002

Genes Dev.

211

128

View full text Add to dashboard Cite

show abstract

“…Early studies reported that CDKN2A gene alterations are either rare or absent in meningiomas. 26 Nevertheless, according to a more recent data reported by Boström et al, 27 homozygous deletions of CDKN2A, CDKN2B and p14ARF genes on the 9p21 were found in 46% of the evaluated anaplastic meningiomas. Additionally, anaplastic meningiomas showed point mutations in CDKN2A and p14ARF or loss of detectable transcripts of these genes.…”

Section: Discussionmentioning

confidence: 93%

Immunohistochemical analysis of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in 271 meningiomas correlation with tumor grade and clinical outcome

Korshunov

Шишкина

Golanov

2003

Intl Journal of Cancer

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Routine pathological examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Numerous efforts have been made for the evaluation of different immunohistochemical assays in meningioma prognosis. We investigated the prognostic significance of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression by immunohistochemical analysis of 271 meningiomas. All tumors were additionally stained for the proliferation markers Ki-67 and DNA topoisomerase II alpha (TopoII␣). Significant differences between the number of p16INK4a-, p18INK4c-and p21CIP1-positive cases were noted among the 3 grades of meningiomas. p16INK4a-and p21CIP-positive tumors were found to prevail among benign meningiomas, whereas p18INK4c immunostaining was closely associated to anaplastic meningiomas. The number of p16INK4a-and p21CIP-positive cases was significantly lower in the cohort of recurrent meningiomas. In contrast, p18INK4c-positive cases were clustered among recurrent meningiomas regardless of tumor grade. Immunoreactivity of p14ARF, p27KIP1 and p73 did not show any differences between meningiomas of various histology and clinical outcomes. Multivariate analysis revealed that only tumor grade and TopoII␣ index are independent criteria for predicting meningioma recurrence. Thus, the immunohistochemical assessment of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in meningiomas does not appear to provide prognostically useful information. Further studies are needed to identify more reliable prognostic markers and to address in more detail the role of cell cycle aberrations in these tumors.

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Section: Chromosome 14mentioning

confidence: 99%

“…80,81 Indeed, abnormalities in chromosome 14 are seen in 100% of grade 3 meningiomas, compared with 31% of grade 1 tumors. 80,81 The strongly increased frequency of 14q deletions in tumors of higher grade suggests an involvement in meningioma progression. A recent study demonstrated that deletions on this chromosome arm were an independent adverse prognostic parameter, which when combined with histological grade and patient age could identify patients at increased risk of relapse.…”

Section: Chromosome 14mentioning

confidence: 99%

Molecular Biology of Unreresectable Meningiomas: Implications for New Treatments and Review of the Literature

et al. 2008

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Even though meningiomas are most often benign tumors, they can be locally invasive and can develop in locations that prevent surgical treatment. The molecular and biologic factors underlying meningioma development are only now beginning to be understood. Genetic factors such as mutations in the neurofibromatosis-2 gene and in chromosomes 1, 9, and 10 play important roles in meningioma development and may be responsible for atypical tumors in some cases. Cellular factors such as telomerase activation and tyrosine kinase receptor mutations may also play an important role. Finally, autocrine and paracrine factors including epidermal growth factor receptor, platelet-derived growth factor-1, and fibroblast growth factor have been implicated in the development of some tumors. Although the relationship between the various factors implicated in tumor development is unknown, understanding these factors will be critical in the treatment of malignant or surgically inaccessible tumors.

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Analysis of cell cycle regulators: p16INK4A, pRb, and CDK4 in low- and high-grade meningiomas

Cited by 33 publications

References 19 publications

Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse

Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse

Immunohistochemical analysis of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in 271 meningiomas correlation with tumor grade and clinical outcome

Molecular Biology of Unreresectable Meningiomas: Implications for New Treatments and Review of the Literature

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