Chromosome 1q gain is not associated with a poor outcome in childhood medulloblastoma: Requirements for the validation of potential prognostic biomarkers

Clifford, Steven C.; O'Toole, K; Ellison, David W.

doi:10.4161/cc.8.5.7709

Cited by 4 publications

(3 citation statements)

References 2 publications

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“…54 In another study comprising 73 cases, evidence for relationship between chromosome 1q gain and poor survival was not detected. 21 In our study, we found no difference in survival in patients with and without chromosome 1q aberration.…”

Section: Discussioncontrasting

confidence: 57%

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The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis

Xia

et al. 2017

Laboratory Investigation

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Medulloblastoma (MB) is the most common malignant brain tumor in childhood. At present, there is no well-established targeted drug for majority of patients. The kinesin family member 14 (KIF14) is a novel oncogene located on chromosome 1q and is dysregulated in multiple cancers. The objectives of this study were to evaluate KIF14 expression and chromosome 1q copy number in MB, and to delineate its biological functions in MB pathogenesis. By quantitative RT-PCR and immunohistochemistry, we found KIF14 was overexpressed in MB. Increased KIF14 expression at protein level was strongly associated with shorter progression-free survival (P=0.0063) and overall survival (P=0.0083). Fluorescence in situ hybridization (FISH) analysis confirmed genomic gain of chromosome 1q in 17/93 (18.3%) of MB. Combined genetic and immunohistochemical analyses revealed that 76.5% of MB with 1q gain showed consistent overexpression of KIF14, and a tight link between chromosome 1q gain and KIF14 overexpression (P=0.03). Transient, siRNAs-mediated downregulation of KIF14 suppressed cell proliferation and induced apoptosis in two MB cell lines. Stably KIF14 knockdown by shRNAs inhibited cell viability, colony formation, migration and invasion, and tumor sphere formation in MB cells. We conclude that KIF14 is dysregulated in MB and is an adverse prognostic factor for survival. Furthermore, KIF14 is part of MB biology and is a potential therapeutic target for MB.

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Section: Discussioncontrasting

confidence: 57%

“…Similar finding showing the lack of chromosome 1q abnormality and adverse clinical outcome has been reported. 21 The results suggest that chromosome 1q aberration contributes to KIF14 upregulation and it is a common event in MB.…”

Section: Gain Of Chromosome 1q Is a Frequentmentioning

confidence: 88%

The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis

Xia

et al. 2017

Laboratory Investigation

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“…Over the past three decades, multiple markers have been developed that hold promise for better prognostic stratification and more individualized therapy for pediatric MB [6][7][8][9]. Recent gene-expression profiling studies have suggested four molecular subtypes of MB, each of which is characterized by a distinct genetic profile, distinct activation of oncogenic pathways, and varied clinical outcomes.…”

Section: Introductionmentioning

confidence: 98%

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Cimmino¹,

Scoppettuolo²,

Carotenuto³

et al. 2011

J Neurooncol

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Medulloblastoma is one of the leading causes of morbidity and mortality in pediatric cancer. Wnt-active tumors, an independent molecular subgroup in medulloblastoma, are characterized by a distinct pattern of genomic aberrations. We assessed the anticancer activity of cantharidin and norcantharidin against medulloblastoma, as cell lines in vitro and in athymic nude mice in vivo. Cantharidin and norcantharidin treatment impaired the growth of DAOY and UW228 medulloblastoma cells and promoted the loss of β-catenin activation and the β-catenin nuclearization linked to N-cadherin impairment in vitro. Intra-peritoneal administration of norcantharidin inhibited the growth of intra-cerebellum tumors in orthotopic xenograft nude mice. Analysis of the xenograft tissues revealed enhanced neuronal differentiation and reduced β-catenin expression. Our findings suggest that norcantharidin has potential therapeutic applications in the treatment of medulloblastoma as a result of its ability to cross the blood-brain barrier and its impairment of Wnt-β-catenin signaling.

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Integrated Molecular Genetic Profiling of Pediatric High-Grade Gliomas Reveals Key Differences With the Adult Disease

Paugh

Jones

et al. 2010

JCO

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568

598

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A B S T R A C T PurposeTo define copy number alterations and gene expression signatures underlying pediatric high-grade glioma (HGG). Patients and MethodsWe conducted a high-resolution analysis of genomic imbalances in 78 de novo pediatric HGGs, including seven diffuse intrinsic pontine gliomas, and 10 HGGs arising in children who received cranial irradiation for a previous cancer using single nucleotide polymorphism microarray analysis. Gene expression was analyzed with gene expression microarrays for 53 tumors. Results were compared with publicly available data from adult tumors. ResultsSignificant differences in copy number alterations distinguish childhood and adult glioblastoma. PDGFRA was the predominant target of focal amplification in childhood HGG, including diffuse intrinsic pontine gliomas, and gene expression analyses supported an important role for deregulated PDGFR␣ signaling in pediatric HGG. No IDH1 hotspot mutations were found in pediatric tumors, highlighting molecular differences with adult secondary glioblastoma. Pediatric and adult glioblastomas were clearly distinguished by frequent gain of chromosome 1q (30% v 9%, respectively) and lower frequency of chromosome 7 gain (13% v 74%, respectively) and 10q loss (35% v 80%, respectively). PDGFRA amplification and 1q gain occurred at significantly higher frequency in irradiation-induced tumors, suggesting that these are initiating events in childhood gliomagenesis. A subset of pediatric HGGs showed minimal copy number changes. ConclusionIntegrated molecular profiling showed substantial differences in the molecular features underlying pediatric and adult HGG, indicating that findings in adult tumors cannot be simply extrapolated to younger patients. PDGFR␣ may be a useful target for pediatric HGG, including diffuse pontine gliomas.

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Chromosome 1q gain is not associated with a poor outcome in childhood medulloblastoma: Requirements for the validation of potential prognostic biomarkers

Abstract: (2009) Chromosome 1q gain is not associated with a poor outcome in childhood medulloblastoma: Requirements for the validation of potential prognostic biomarkers,

Cited by 4 publications

References 2 publications

The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis

The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Integrated Molecular Genetic Profiling of Pediatric High-Grade Gliomas Reveals Key Differences With the Adult Disease

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