Abstract: Objective To detect the gene mutations in patients with Adenocarcinoma at esophagogastric junction(AEG) and to analyze the effect of Involucrin (IVL) mutation on the biological function of tumor cells. Methods Whole exome sequencing was performed on cancerous and paired adjacent normal tissues from 22 AEG patients in Shanxi province. IVL was selected for further investigation of mutation sites. Esophagus cancer data from TCGA were divided into three groups based on IVL mutations. Differentially-expressed genes were screened and proceeded via Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Cell proliferation and migration assays were performed to evaluate the effect of over-expression of IVL on KYSE 150 cells. Mutant IVL oligopeptides were synthesized and used to evaluate the binding activity with TGase1. Results Five IVL mutation sites were identified in 22 AEG. GO annotation indicated that these mutations were related to the epithelial differentiation and activity of cell differentiation regulation. KEGG analysis demonstrates that IVL mutations are associated with cAMP signaling pathway. IVL over-expression inhibits the proliferation and migration of esophageal cancer cells(P＜0.05). In addition, Q439H mutant IVL oligopeptides shows lower binding affinity to TGase1 than wild-type oligopeptides. Conclusions The seventh amino acid mutation in IVL repeat motif does weaken IVL binding to TGase1. This mutation may affect tumor-related biological processes and signaling pathways.

Key words: adenocarcinoma at esophagogastric junction, Involucrin, gene mutation