MET overexpressing chordomas frequently exhibit polysomy of chromosome 7 but no MET activation through sarcoma-specific gene fusions

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.

Regulation of MET-mediated proliferation of thyroid carcinoma cells by miR-449b

“…MET plays a critical role during embryogenesis and tissue repair and remodeling in adults [8]. Aberrant activation of MET has been detected in various cancers [9][10][11][12][13][14], including TC [15,16]. Nevertheless, its regulation in TC remains elusive.…”

Effects of Isomerization on the Measured Thermochemical Properties of Deprotonated Glycine/Protic‐Solvent Clusters

“…Furthermore, when considering that T is crucial in notochordal development, and that the anatomical site at which chordomas arise co‐localizes to the site at which fetal notochord exists, we postulate that there is a strong argument that aberrant expression of T plays a major role in the pathogenesis of this disease 19. Finally, the finding in this study that polysomy 6 is more common than that reported for other chromosomes, other than chromosome 7, 2 and 21, adds weight to the postulate that T is targeted in this CNG rather than there being genome‐wide gain in copy number 4, 15–17, 20, 21. However, the finding that the percentage of cells with CNG of the T locus within a chordoma was often not > 50% implies that, in at least some cases, alteration of T is not the primary event in the development of this tumour.…”

Silencing of c-Met by RNA interference inhibits the survival, proliferation, and invasion of nasopharyngeal carcinoma cells

“…c-Met is a tyrosine kinase receptor for HGF and overexpressed in a variety of malignant tumors [18], such as chordomas [19], gastrointestinal tract [20], and thyroid Fig. 3 Depletion of c-Met inhibits the migration and invasion of CNE-2 cells.…”