Aberrant DNA methylation of ESR1 and p14ARF genes could be useful as prognostic indicators in osteosarcoma

Osteosarcoma (OS) is the eighth most common form of childhood and adolescence cancer. Approximately 10%-20% of patients present metastatic disease at diagnosis and the 5-year overall survival remains around 70% for nonmetastatic patients and around 30% for metastatic patients. Metastatic disease at...

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Published inOncoTargets and therapy Vol. 6; pp. 713 - 723
Main Authors Sonaglio, Viviane, de Carvalho, Ana C, Toledo, Silvia R C, Salinas-Souza, Carolina, Carvalho, André L, Petrilli, Antonio S, de Camargo, Beatriz, Vettore, André L
Format Journal Article
LanguageEnglish
Published New Zealand Taylor & Francis Ltd 01.01.2013
Dove Press
Dove Medical Press
Subjects
Bone cancer
Deoxyribonucleic acid
DNA
DNA methylation
ESR1
hypermethylation
Medical prognosis
Metastasis
Original Research
osteosarcoma
p14ARF
Sarcoma
DNA methylation
p14ARF
ESR1
osteosarcoma
hypermethylation
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Summary:Osteosarcoma (OS) is the eighth most common form of childhood and adolescence cancer. Approximately 10%-20% of patients present metastatic disease at diagnosis and the 5-year overall survival remains around 70% for nonmetastatic patients and around 30% for metastatic patients. Metastatic disease at diagnosis and the necrosis grade induced by preoperative treatment are the only well-established prognostic factors for osteosarcoma. The DNA aberrant methylation is a frequent epigenetic alteration in humans and has been described as a molecular marker in different tumor types. This study evaluated the DNA aberrant methylation status of 18 genes in 34 OS samples without previous chemotherapy treatment and in four normal bone specimens and compared the methylation profile with clinicopathological characteristics of the patients. We were able to define a three-gene panel (AIM1, p14ARF, and ESR1) in which methylation was correlated with OS cases. The hypermethylation of p14ARF showed a significant association with the absence of metastases at diagnoses, while ESR1 hypermethylation was marginally associated with worse overall survival. This study demonstrated that aberrant promoter methylation is a common event in OS and provides evidence that p14ARF and ESR1 hypermethylation could be useful as a prognostic indicator for this disease.
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ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S44918