C-MYC expression in medulloblastoma and its prognostic value

Herms, Jochen; Neidt, Iris; Lüscher, Bernhard; Sommer, Anette; Schürmann, Peter; Schröder, T.; Bergmann, Markus; Wilken, Bernd; Probst-Cousin, Stephan; Hernáiz‐Driever, Pablo; Behnke, J.; Hanefeld, F.; Pietsch, Torsten; Kretzschmar, Hans A.

doi:10.1002/1097-0215(20000920)89:5<395::aid-ijc1>3.0.co;2-v

Cited by 148 publications

(84 citation statements)

References 32 publications

(43 reference statements)

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“…Some of the tumors may not correlate with the conventional and well-characterized lesions observed in human patients or, alternatively, these tumors could correspond to some rare and poorly characterized types of human tumors. Nevertheless, most of the tumors detected during this study could be characterized by hematoxylin and eosin (H&E) staining and some expressed typical molecular markers-for example, mutant KRAS in the rhabdomyosarcoma (27,28) and MYC in the medulloblastoma (29,30).…”

Section: Discussionmentioning

confidence: 94%

A DNA transposon-based approach to validate oncogenic mutations in the mouse

Prosser

Campos

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified putative cancer associated loci. Functional validation of these genetic mutations in vivo is becoming a challenge. We describe here a DNA transposon-based platform that permits us to explore the oncogenic potential of genetic mutations in the mouse. Briefly, promoter-less human cancer gene cDNAs were first cloned into Sleeping Beauty (SB) transposons. DNA transposition in the mouse that carried both the transposons and the SB transposase made it possible for the cDNAs to be expressed from an appropriate endogenous genomic locus and in the relevant cell types for tumor development. Consequently, these mice developed a broad spectrum of tumors at very early postnatal stages. This technology thus complements the large-scale cancer genome projects.

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Section: Discussionmentioning

confidence: 94%

A DNA transposon-based approach to validate oncogenic mutations in the mouse

Prosser

Campos

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…30 Coexpression of HER2 and HER4, two members of the epidermal growth factor receptor family, showed independent prognostic significance in a series of 70 patients with childhood medulloblastoma. 31 Low mRNA expression of the oncogene c-MYC 32,33 and elevated expression of the neurotrophin-3 receptor TrkC 34 (which promotes apoptosis in medulloblastoma) have recently been reported to be associated with a favorable clinical outcome. In addition, aberrant expression of Erb-2, a tyrosine kinase 1 receptor, could also be involved in the pathogenesis of human medulloblastomas through the formation of a neuregulin/Erb-2 autocrine loop.…”

Section: Discussionmentioning

confidence: 99%

Calbindin‐D_28k

Pelc¹,

Vincent

Ruchoux

et al. 2002

Cancer

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BACKGROUNDThe expression of the Ca2+‐binding protein calbindin‐D28k was analyzed in medulloblastomas in relation to clinical features and other biologic markers related to cell proliferation, differentiation, p53, and cerebellar developmental regulated gene expression.METHODSImmunohistochemistry was carried out on histologic slides from a first retrospective series of 29 nonmetastatic and 10 metastatic medulloblastoma formalin‐fixed, paraffin‐embedded tissues, using specific antibodies against calbindin‐D28k, calretinin, α‐parvalbumin and β‐parvalbumin, and S100 proteins. Informed consent was obtained from the subjects and/or guardians. Other biologic markers for differentiation, cell proliferation, the expression of the p53 tumor suppressor gene protein, and cerebellar developmental regulated genes were similarly investigated. A second series of 16 medulloblastomas from young patients (younger than 15 years) was added in order to validate the results obtained in the first series.RESULTSOf all the markers investigated, only calbindin‐D28k was significantly associated with prognosis. Survival and remission (i.e. recurrence free) time analysis performed on all the cases (n = 55) confirmed a high risk of death (P = 0.004) and recurrence (P = 0.003) associated with calbindin‐positivity. As calbindin‐positivity was predominantly observed in tumors from young patients, the authors confirmed its prognostic value in the subgroup of patients younger than 15 years (n = 37). Cox regression analysis showed a significant and independent prognostic value for calbindin expression and, to a lesser extent, the type of surgery (total or subtotal). Three risk groups were thus identified, distinguishing among the cases characterized by a total resection and calbindin‐negativity (good prognosis), by a subtotal resection and calbindin‐negativity (intermediary), and by calbindin‐positivity (bad prognosis).CONCLUSIONSThe current study suggests that calbindin‐positive medulloblastomas represent a subclass of aggressive tumors more frequently seen in younger patients. Cancer 2002;95:410–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10666

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“…Both medulloblastoma and neuroblastoma belong to the most challenging oncologic diseases of childhood and serve as useful models for development of targeted therapy based on novel biological understanding. Amplification of the MYCN oncogene characterizes the subset of most aggressive neuroblastomas [6], whereas in medulloblastoma, activation of the c-MYC oncogene has been shown to be one of the most reliable prognostic factors [9,10]. Even though MYCN-amplification also occurs in medulloblastoma, its value as a prognostic factor has not been clearly established ( [10] and reviewed in [11]).…”

Section: Eglmentioning

confidence: 99%

Embryonal neural tumours and cell death

et al. 2009

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Medulloblastoma and neuroblastoma are malignant embryonal childhood tumours of the central and peripheral nervous systems, respectively, which often show poor clinical prognosis due to resistance to current chemotherapy. Both these tumours have deficient apoptotic machineries adopted from their respective progenitor cells. This review focuses on the specific background for tumour development, and highlights biological pathways that present potential targets for novel therapeutic approaches.

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C-MYC expression in medulloblastoma and its prognostic value

Cited by 148 publications

References 32 publications

A DNA transposon-based approach to validate oncogenic mutations in the mouse

A DNA transposon-based approach to validate oncogenic mutations in the mouse

Calbindin‐D_28k

Embryonal neural tumours and cell death

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C-MYC expression in medulloblastoma and its prognostic value

Cited by 148 publications

References 32 publications

A DNA transposon-based approach to validate oncogenic mutations in the mouse

A DNA transposon-based approach to validate oncogenic mutations in the mouse

Calbindin‐D28k

Embryonal neural tumours and cell death

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Calbindin‐D_28k