Spindle assembly checkpoint gene expression in childhood adrenocortical tumors (ACT): Overexpression of Aurora kinases A and B is associated with a poor prognosis

ABSTRACT Background Pediatric adrenocortical tumors (ACT) are rare malignancies and treatment has a small impact on survival in advanced disease and the discovery of potential target genes could be important in new therapeutic approaches. Methods The mRNA expression levels of spindle checkpoint gene...

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Bibliographic Details
Published in:Pediatric blood & cancer 2013-11, Vol.60 (11), p.1809-1816
Main Authors: Borges, Kleiton Silva, Moreno, Daniel Antunes, Martinelli Jr, Carlos Eduardo, Antonini, Sonir Roberto Rauber, de Castro, Margaret, Tucci Jr, Silvio, Neder, Luciano, Ramalho, Leandra Naira Zambelli, Seidinger, Ana Luiza, Cardinalli, Izilda, Mastellaro, Maria José, Yunes, José Andres, Brandalise, Silvia Regina, Tone, Luiz Gonzaga, Scrideli, Carlos Alberto
Format: Article
Language:English
Subjects:
Adolescent
Adrenocortical Carcinoma - enzymology
Adrenocortical Carcinoma - genetics
Adrenocortical Carcinoma - pathology
adrenocortical tumor
Antineoplastic Agents - pharmacology
AURK
Aurora Kinase A
Aurora Kinase B
Aurora Kinases
Benzamides - pharmacology
Cell Proliferation - drug effects
Cells, Cultured
Child
Child, Preschool
childhood
Disease-Free Survival
Enzyme Inhibitors - pharmacology
Female
Gene expression
Hematology
Humans
Immunohistochemistry
Infant
Kaplan-Meier Estimate
Kinases
M Phase Cell Cycle Checkpoints - genetics
Male
Oncology
Pediatrics
Prognosis
Proportional Hazards Models
Protein-Serine-Threonine Kinases - biosynthesis
Protein-Serine-Threonine Kinases - genetics
Quinazolines - pharmacology
Real-Time Polymerase Chain Reaction
RNA, Messenger - analysis
spindle assembly checkpoint genes
Transcriptome
Tumors
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Summary:ABSTRACT Background Pediatric adrenocortical tumors (ACT) are rare malignancies and treatment has a small impact on survival in advanced disease and the discovery of potential target genes could be important in new therapeutic approaches. Methods The mRNA expression levels of spindle checkpoint genes AURKA, AURKB, BUB, and BUBR1 were analyzed in 60 children with ACT by quantitative real time PCR. The anticancer effect of ZM447439, an experimental AURK inhibitor, was analyzed in a primary childhood ACT culture carrying the TP53 p.R337H mutation. Results A significant association was observed between malignancy as defined by Weiss score ≥3 and higher AURKA (2.0‐fold, P = 0.01), AURKB (7.0‐fold, P = 0.007), and BUBR1 (5.8‐fold, P = 0.007) gene expression, and between unfavorable event (death or relapse) and higher expression of AURKA (6.0‐fold, P = 0.034) and AURKB (17‐fold, P = 0.013). Overexpression of AURKA and AURKB was associated with lower event‐free survival in uni‐ (P 
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.24653