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.
Keywords: gastric cancer, next-generation sequencing, copy number variations, overall survival