Chordomas are rare mesenchymal
tumors occurring exclusively in the midline from clivus to sacrum. Early
tumor detection is extremely important as these
tumors are resistant to
chemotherapy and irradiation. Despite continuous research efforts surgical excision remains the main treatment option. Because of the often challenging anatomic location early detection is important to enable complete
tumor resection and to reduce the high incidence of local recurrences. The aim of this study was to explore whether DNA methylation, a well known epigenetic marker, may play a role in
chordoma development and if hypermethylation of specific CpG islands may serve as potential
biomarkers correlated with SNP analyses in
chordoma. The study was performed on
tumor samples from ten
chordoma patients. We found significant
genomic instability by Affymetrix 6.0. It was interesting to see that all
chordomas showed a loss of 3q26.32 (PIK 3CA) and 3q27.3 (BCL6) thus underlining the potential importance of the PI3K pathway in
chordoma development. By using the AITCpG360 methylation assay we elucidated 20 genes which were hyper/hypomethylated compared to normal blood. The most promising candidates were nine hyper/hypomethylated genes C3, XIST, TACSTD2, FMR1, HIC1, RARB, DLEC1, KL, and RASSF1. In summary, we have shown that
chordomas are characterized by a significant
genomic instability and furthermore we demonstrated a characteristic DNA methylation pattern. These findings add new insights into
chordoma development, diagnosis and potential new treatment options.