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.