Recurrent Chromosomal Copy Number Alterations in Chordoma
GP Nielsen, V Deshpande, AE Rosenberg, JM Batten, F Hornicek, J Iafrate. Massachusetts General Hospital, Boston, MA
Background: Chordoma is an uncommon neoplasm with the vast majority arising in the axial skeleton. Most originate in the sacrum, followed by the skull base and the mobile spine. Morphologically, immunohistochemically and ultrastructrually, chordoma phenotypically recapitulates the normal notochord and it has been postulated that they arise from notochordal rests and benign notochordal cell tumors. A variety of chromosomal abnormalities have been identified in chordomas, however, there is little CGH date on chordomas.
Design: Frozen tumor was obtained from 17 chordomas. H&E slides of each tumor sample was analyzed to ensure a high proportion of tumor cells. Genomic DNA was extracted from frozen tissue using the Gentra Puregene isolation kit. We analyzed tumor genome-wide copy number alterations using array comparative genomic hybridization (array CGH). Agilent 244k oligonucleotide arrays were hybridized with tumor DNA labeled in CY5 and control normal DNA labeled in CY3. Signals were captured using an Agilent microarray scanner, and data analyzed using CGH analytics software. High-quality copy number data was produced for all tumors, with copy number gains or losses defined as log2 rations of greater or less than 2 standard deviations. Based on the CGH results immunohistochemical stains for p16 were done on 12 additional chordomas to determine if there was loss of expression.
Results: The patient population ranged in age from 41 to 83 (average 59) years. The tumors were all conventional chordomas by light microscopy and were located in the sacrum, skull base and mobile spine. By CGH the most common abnormality was loss of 1p that was found in all tumors. Loss of 9p (CDKN2A; p16) or chromosome 9 was identified in 15 out of 17 (88%), tumors with homozygous deletion in four tumors. Other common changes included losses of 3p, 4, 10, 13, 14, 18, and 22. Gains were rare and included gains of chromosome 7 (3/14) and 19p (4/14). Immunohistochemical stain for p16 showed no staining in any of the tumors.
Conclusions: Various but overall consistent chromosomal abnormalities are present in chordomas. Frequent loss of 1p and 9p suggest the presence of a tumor suppressor genes that might be important in the pathogenesis of chordoma. The results suggest that p16 is a candidate tumor suppressor gene involved in the pathogenesis of chordoma.
Category: Bone & Soft Tissue
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 16, Tuesday Morning