Analysis of the relative copy numbers of TP63, YAP1 and KMT2D genetic loci and EGFR expression in orthotopic patient-derived xenografts of cardioesophageal cancer in immunodeficient mice.

Abstract

e15033 Background: Cardioesophageal cancer is a common tumor affecting the cardiac stomach and lower esophagus. Tumor heterogeneity is important, since it can cause the ineffectiveness of chemotherapy and radiotherapy due to individual characteristics of the neoplasm in different patients, as well as the intensification of invasion and metastasis. Our purpose was to analyze the relative copy numbers of TP63, YAP1 and KMT2D genetic loci and EGFR expression in orthotopic patient-derived xenografts of cardioesophageal cancer. Methods: The model of cardioesophageal cancer was created in Balb/c Nude mice with surgical bioptates of adenocarcinoma obtained from donors. The relative copy numbers of TP63, YAP1 and KMT2D genetic loci and EGFR expression were determined by Real-Time qPCR. Results: A PDX model of cardioesophageal cancer was successfully created by transplanting a moderately differentiated adenocarcinoma from a patient diagnosed with infiltrative ulcerative cancer of the lower third of the esophagus with a transition to the cardiac stomach into the distal esophagus of Balb/c Nude mice. The EGFR expression was elevated in patient tumor samples, compared to healthy tissues (p = 0.021) and gastric cancer xenografts (p = 0.07). Molecular genetic analysis demonstrated an association between an increased EGFR expression and changes in the relative copy numbers of TP63, YAP1, and KMT2D in donor samples compared to gastric cancer xenografts (p = 0.02, p = 0.026 and p = 0.042). Conclusions: The relative copy numbers of TP63, YAP1, and KMT2D were associated with intensified EGFR expression and changed with each new generation of orthotopic xenografts.