title: Chordoma characterization of significant changes of the DNA methylation pattern.
abstract: 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.
authors.affiliation: Center for Medical Research, Medical University Graz, Graz, Austria. beate.rinner@medunigraz.at
authors.forename: Beate
authors.initials: B
authors.lastname: Rinner
authors.forename: Andreas
authors.initials: A
authors.lastname: Weinhaeusel
authors.forename: Birgit
authors.initials: B
authors.lastname: Lohberger
authors.forename: Elke Verena
authors.initials: EV
authors.lastname: Froehlich
authors.forename: Walter
authors.initials: W
authors.lastname: Pulverer
authors.forename: Carina
authors.initials: C
authors.lastname: Fischer
authors.forename: Katharina
authors.initials: K
authors.lastname: Meditz
authors.forename: Susanne
authors.initials: S
authors.lastname: Scheipl
authors.forename: Slave
authors.initials: S
authors.lastname: Trajanoski
authors.forename: Christian
authors.initials: C
authors.lastname: Guelly
authors.forename: Andreas
authors.initials: A
authors.lastname: Leithner
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D002817:Chordoma / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D051860:Fragile X Messenger Ribonucleoprotein 1; D051741:Kruppel-Like Transcription Factors; D062085:RNA, Long Noncoding; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C119064:DLEC1 protein, human; C497683:FMR1 protein, human; C499808:HIC1 protein, human; C411762:RASSF1 protein, human; C499380:TACSTD2 protein, human; C077885:XIST non-coding RNA; C082925:retinoic acid receptor beta