Molecular profiling of chordoma.
The molecular basis of chordoma is still poorly understood, particularly with respect to differentially expressed genes involved in the primary origin of chordoma. In this study, therefore, we compared the transcriptional expression profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U-CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high-density oligonucleotide array. The expression of 65 genes whose mRNA levels differed significantly (p<0.001; ≥6-fold change) between chordoma and control (vertebral disc) was identified. Genes with increased expression in chordoma compared to control and chondrosarcoma were most frequently located on chromosomes 2 (11%), 5 (8%), 1 and 7 (each 6%), whereas interphase cytogenetics of 33 chordomas demonstrated gains of chromosomal material most prevalent on 7q (42%), 12q (21%), 17q (21%), 20q (27%) and 22q (21%). The microarray data were confirmed for selected genes by quantitative polymerase chain reaction analysis. As in other studies, we showed the expression of brachyury. We demonstrate the expression of new potential candidates for chordoma tumorigenesis, such as CD24, ECRG4, RARRES2, IGFBP2, RAP1, HAI2, RAB38, osteopontin, GalNAc-T3, VAMP8 and others. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in chordoma.
Institute of Pathology, University Hospitals of Ulm, Germany.
Stefanie
S
Scheil-Bertram
Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilian University of Munich, Munich, Germany.
Roland
R
Kappler
Department of Orthopedic Trauma, Hand and Reconstructive Surgery, University Hospitals of Ulm, Germany.
Alexandra
A
von Baer
Department of Trauma, Hand and Reconstructive Surgery, Ev. Diakonissenanstalt, Karlsruhe, Germany.
Erich
E
Hartwig
Department of Trauma and Reconstructive Surgery, Karl-Olga-Krankenhaus, Stuttgart, Germany.
Michael
M
Sarkar
Laboratory of Experimental Oncology, Orthopedic Rizzoli Institute, Bologna, Italy.
Massimo
M
Serra
Institute of Pathology, University Hospitals of Ulm, Germany.
Silke
S
Brüderlein
Department of Orthopedics, University of Düsseldorf, Germany.
Bettina
B
Westhoff
Institute of Pathology, University Hospitals of Ulm, Germany.
Ingo
I
Melzner
Institute of Pathology, University of Giessen, Germany.
Birgit
B
Bassaly
Department of Translational Brain Research, DZNE (German Center for Neurodegenerative Diseases) and Ludwig-Maximilian University of Munich, Munich, Germany.
Jochen
J
Herms
Department of Neurosurgery, University of Kiel, Kiel, Germany.
Heinz-Hermann
HH
Hugo
Department of Trauma and Orthopedic Surgery, Diakoniekrankenhaus, Rotenburg (Wümme), Germany.
Michael
M
Schulte
Institute of Pathology, University Hospitals of Ulm, Germany.
Peter
P
Möller
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000235:genetics* / Q000473:pathology; D002817:Chordoma / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics*; D000098908:Brachyury Protein
D014408:Biomarkers, Tumor; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein