[54] The Benign Notochordal Cell Tumor and Ecchordosis Physaliphora Lack the Complex Genomic and Genetic Alterations Commonly Found in the Conventional Chordomas

Yang D Lee, Long P Le, Vikram Deshpande, Anthony J Iafrates, Andrew E Rosenberg, G Petur Nielsen. Massachusetts General Hospital, Boston, MA; University of Miami, Miami

Background: Chordoma is a low-grade malignant neoplasm of the axial skeleton, with a histological appearance similar to the notochord present in early embryogenesis. Previous analyses of chordoma using cytogenetics, flouresecent in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) have revealed heterogenous and complex alterations including chromosomal-scale loss and gain, focal gene amplifications, translocations, and chromotripses. Although some of these complex alterations can contribute to the malignant nature of chordoma, the majority of these genomic changes likely represent either late events of tumorigenesis or passenger mutations caused by genomic instability. The early origin of chordoma has remained enigmatic although there is evidence that they arise from a precursor lesion - benign notochordal cell tumor (BNCT). BNCTs share certain cytologic similarities to the conventional chordoma and may be distinguished from the latter morphologically, albeit at times this is very challenging. Another related notochordal lesion is ecchordosis physaliphora (EP). EPs are basilar-pontine lesions which also share histological similarities to the conventional chordoma. But unlike chordoma, they are often discovered incidentally during autopsy, and are thought to be notochordal vestiges remained from embryogenesis. It is currently unknown whether EPs can, in rare instances, develop into chordoma.
Design: Genomic DNA was extracted from formalin-fixed paraffin-embedded specimen of BNCTs and EPs and analyzed using aCGH for copy number changes.
Results: Preliminary aCGH data showed that a benign notochordal cell tumor and an ecchordosis physaliphora lack the complex genomic alteration seen in the majority of conventional chordomas, and instead contain more focal copy number changes at several loci. Furthermore, the aCGH data showed no loss of p16 or PTEN, and no amplification of brachyury, changes commonly detected in chordomas.
Conclusions: Our aCGH results suggest that the deletion of p16 and PTEN loci, the amplification of brachyury gene, and the complex genomic alterations are relatively late events in the pathogenesis of chordoma, and opens the possibility that other unexplored alterations may be important in the early tumorigenesis of chordoma.
Category: Bone & Soft Tissue

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 2, Tuesday Morning


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