MET overexpressing chordomas frequently exhibit polysomy of chromosome 7 but no MET activation through sarcoma-specific gene fusions
| Autor: | Sebastian Bauer, Margarethe Konik, Florian Grabellus, Johannes van de Nes, Karl Worm, Sien-Yi Sheu, Kurt Werner Schmid, Rupert Egensperger, Werner Paulus |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Adolescent Medizin Aneuploidy Biology Polysomy 7 Fusion gene Young Adult Chordoma medicine Humans Child Aged Aged 80 and over Chromosome 7 (human) Polysomy Tissue microarray medicine.diagnostic_test Sarcoma General Medicine Middle Aged Proto-Oncogene Proteins c-met medicine.disease Molecular biology Female Gene Fusion Chromosomes Human Pair 7 Fluorescence in situ hybridization |
| Zdroj: | Tumor Biology. 31:157-163 |
| ISSN: | 1423-0380 1010-4283 |
| DOI: | 10.1007/s13277-010-0021-0 |
| Popis: | Overexpression of MET and polysomy 7 was formerly demonstrated in chordomas. We investigated mesenchymal-epithelial transition factor (MET) protein expression and copy numbers of chromosome 7 in human chordomas. Furthermore, tumors were screened for gene fusions (PAX3-FKHR, ASPL-TFE3, and SYT-SSX) previously shown to be associated with MET activation in sarcomas. Tissue microarrays (TMAs) were constructed from 66 chordoma samples. MET protein expression was assessed by immunohistochemistry using an immunoreactive score (IRS, scores 0-12). fluorescence in situ hybridization (FISH) with a dual-color DNA probe (7q31) for MET amplification was performed on TMA sections and RT-PCR for PAX3-FKHR, ASPL-TFE3 (type 1 + 2), and SYT-SSX (type 1 + 2) gene fusions on punch biopsies. All tumors (n = 66) expressed MET protein. FISH analysis of 33 tumors lacked MET gene amplification but showed polysomy of chromosome 7 in 15 (45.5%) tumors (13 low and two high polysomies). Although, polysomy 7 showed an increasing incidence with escalating MET IRS, this finding was not statistically significant. PAX3-FKHR, ASPL-TFE3, or SYT-SSX gene fusions were not demonstrable (n = 52). We found MET protein expression in all chordomas. A clear influence of polysomy 7 on MET protein expression could not be statistically demonstrated for this cohort. Moreover, gene fusions with the ability to cause MET overexpression do not occur in chordomas. |
| Databáze: | OpenAIRE |
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