Abstract
Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control. We identified 27 mutated genes, of which 19 genes are reported in COSMIC database (ZNF208, CRNN, ATXN3, DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17, JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121, AKAP2, ACAN and ACADL), and eight genes have not previously been described in gastric cancer (CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2, DMBT1and DAB1).Additionally,GPX4 and MPND in 19q13.3-13.4 region, is characterized as a novel fusion-gene. This study disclosed novel biological markers and tumorigenic pathways that would predict gastric cancer occurring peritoneal metastasis.
Highlights
Influence of Peritoneal metastasis (PM) on survival, efforts should be undertaken to explore the possible molecular mechanisms and preventing or treating strategies
Over the past few years, advances of next generation sequencing (NGS) and affordable price have resulted in increased cancer genome studies, which are of great helpfulness to investigate pathogenesis, driver genes, molecular classification and drug targets for human gastric cancer[8]
The subject was diagnosed as gastric cancer occurring peritoneal metastasis before operation by computerized tomography (CT) scan of abdominal region as well as intraoperative observation (Fig. 1A,B)
Summary
Influence of PM on survival, efforts should be undertaken to explore the possible molecular mechanisms and preventing or treating strategies. Wang′ s group performed whole-genome sequencing in 100 tumor-normal pairs of gastric cancer and identified significantly mutated driver genes (MUC6, CTNNA2, GLI3, RNF43 and others)[10]. That is tumors positive for Epstein-Barr virus, microsatellite unstable tumors, genomically stable tumors and chromosomal instability tumors Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies[11]. We describe the clinicopathological features and whole-genome and transcriptome sequencing characterization on a set of precious samples from a paired gastritis, primary gastric cancer, peritoneal metastasis, as well as peripheral blood. Genome-wide screening of whole genome and transcriptome dysregulation between non-cancerous tissues, primary cancer and PM tumor would provide insights into the molecular basis of gastric cancer initiation, progression and metastasis
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