<Emphasis Type="Italic">MET</Emphasis> overexpressing chordomas frequently exhibit polysomy of chromosome 7 but no <Emphasis Type="Italic">MET</Emphasis> activation through sarcoma-specific gene fusions |
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Authors: | Florian Grabellus Margarethe J Konik Karl Worm Sien-Yi Sheu Johannes A P van de Nes Sebastian Bauer Werner Paulus Rupert Egensperger Kurt W Schmid |
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Institution: | 1.Institute of Pathology and Neuropathology,University Hospital of Essen, University of Duisburg-Essen,Essen,Germany;2.Department of Internal Medicine and Cancer Research,University Hospital of Essen, University of Duisburg-Essen,Essen,Germany;3.Institute of Neuropathology,University Hospital Münster,Münster,Germany;4.Center of Neuropathology and Prion Research,Ludwig-Maximilians-University of München,München,Germany |
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Abstract: | 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. |
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