ECTS2016 Poster Presentations Cancer and bone: basic, translational and clinical (37 abstracts)
Conventional and Pagetic Giant Cell Tumor of bone: distinct clinical features are defined by different genetic background and histological appearance
Giuseppina Divisato 1 , Federica Scotto di Carlo 1 , Teresa Esposito 1 , Laura Pazzaglia 2 , Maria Serena Benassi 2 , Daniela Merlotti 3 , Domenico Rendina 4 , Luigi Gennari 4 & Fernando Gianfrancesco 1
1Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, National Research Council of Italy, Naples, Italy; 2Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Bologna, Italy; 3Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; 4Department of Medicine and Surgery, Federico II University, Naples, Italy.
Conventional Giant Cell Tumor of Bone (GCT) is an aggressive bone tumor characterized by malignant mesenchymal stromal cells, responsible for its unusually high population of multinucleated osteoclast-like giant cells. GCT could arise in bones affected by Paget’s disease of bone (GCT/PDB) with a different clinical profile regarding the age-onset of the neoplasm (30 years vs 50 years) and the skeletal localization (appendicular skeleton vs cranio-facial bones), let hyphotesize a different genetic signature for these two forms of the tumor. Somatic mutations in H3F3A were described as a genetic defect of conventional GCT (92%), that we confirmed in our cohort of 44 conventional GCT cases. Recently, using whole-exome sequencing approach in a large PDB pedigree with four cases of GCT/PDB, we identified the c.2810C>G (p.Pro937Arg) missense mutation in the Zinc Finger Protein 687 gene (ZNF687), that precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated GCT/PDB individuals identified the same mutation in all individuals, unravelling a founder effect. The absence of H3F3A mutations in these cases confirmed a different genetic background for GCT and GCT/PDB. We also identified an exquisite correlation between the mutation and the histological appearance of the tumor, with GCT/PDB showing a higher number of osteoclast-like giant cells (twice), with about 50% of nuclei per cell more than conventional GCT. Biochemically, GCT/PDB also showed a different profile as a consequence of the absence of the up-regulation of conventional GCT markers (FGFR2IIIc). In conclusion, the distinct clinical features of pagetic and conventional GCT are associated with different genetic background, resulting in a certain biochemical behaviour and histological appearance of the tumor.
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Bone Abstracts
ISSN 2052-1219 (online)
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