Exon Coverage Variations Between Cancer Tissues and Adjacent Non-Cancerous Tissues are Prognostic Factors in Gastric Cancer

INTRODUCTION: Gastric cancer is highly heterogeneous both clinically and pathologically and is one of the leading causes of cancer-related deaths worldwide. Genomic coverage variations, also known as copy number variations (CNVs), play a critical role in the carcinogenesis of gastric cancer. Many studies have demonstrated that DNA CNVs are important factors affecting the expression of protein-encoding genes in the gastric cancer genome. METHODS: Thirty gastric cancer patients from a Chinese population were enrolled. Genomic DNA was extracted from gastric cancer tissue and matched adjacent non-cancerous tissue from each patient. A panel of 1,021 genes including 3300 exons was designed and subjected to next-generation sequencing. Copy numbers of each gene and exon were calculated for each tissue. Coverage variations between gastric cancer tissue and matched adjacent non-cancerous tissue were also calculated, and we examined the correlation between overall survival of patients and coverage variation type for each exon. RESULTS: DNA from cancerous tissue and corresponding adjacent non-cancerous tissue were significantly different with respect to the pattern of gene copy number. Exon copy numbers were highly consistent among non-cancerous samples and confirmed that non-cancerous tissue contain diploid genomes. In contrast, the gene coverage pattern among cancerous tissue showed significant differences and confirmed that gastric cancer is a genetically heterogeneous disease. Numerous exon coverage variations were identified in gastric cancer tissue compared with matched, adjacent non-cancerous tissue. Overall survival between patients with and without coverage variations in regions of NOTCH2, NTRK3, ERBB2 and RERE exons exhibited significant differences. This is consistent with previous reports and indicates that these findings may have prognostic value. CONCLUSION: Our results confirm that gastric cancer is a genetically heterogeneous disease. Exon coverage variations between cancer tissue and their adjacent non-cancerous tissue were shown to be associated with prognosis in gastric cancer.