PMC:4385186 / 27314-28507 JSONTXT

{"project":"2_test","denotations":[{"id":"25839328-21436442-2052591","span":{"begin":190,"end":192},"obj":"21436442"},{"id":"25839328-23502315-2052592","span":{"begin":464,"end":466},"obj":"23502315"},{"id":"25839328-24260522-2052592","span":{"begin":464,"end":466},"obj":"24260522"}],"text":"Focal CNAs are more likely to contain driver genes that confer clonal advantage, are causally implicated in oncogenesis, and have been positively selected during the evolution of the cancer.33 Therefore, to identify genes affected by recurrent CNAs, we used the Integrative Genomics Viewer to manually inspect the 126 significantly altered regions. This approach identified recurrent focal CNAs, including amplified chromosomal segments containing CBX4 and CBX834,35 (Figure S4B). Amplification of these genes was validated by FISH and qPCR copy-number assay (Figure 2A). Of the 104 ESCC specimens, 39% and 51% of tumors had an immunoreactivity score for CBX4 and CBX8 levels, respectively, which is at least double that of matched normal tissue (TIRS/NIRS \u003e 2; Figure 2B). Moreover, silencing CBX4 and CBX8 in KYSE2 and KYSE510 cells (which harbor high endogenous expression) significantly inhibited cell proliferation, colony formation, and cell invasion (Figures 2C–2E; Figure S6). These results suggest that CBX4 and CBX8 amplification and the resultant protein upregulation contribute to the development of ESCC and that they might thus serve as potential drug targets for ESCC treatment."}