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BackgroundStomach cancer is the third deadliest among all cancers worldwide. Although incidence of the intestinal-type gastric cancer has decreased, the incidence of diffuse-type is still increasing and its progression is notoriously aggressive. There is insufficient information on genome variations of diffuse-type gastric cancer because its cells are usually mixed with normal cells, and this low cellularity has made it difficult to analyze the genome.ResultsWe analyze whole genomes and corresponding exomes of diffuse-type gastric cancer, using matched tumor and normal samples from 14 diffuse-type and five intestinal-type gastric cancer patients. Somatic variations found in the diffuse-type gastric cancer are compared to those of the intestinal-type and to previously reported variants. We determine the average exonic somatic mutation rate of the two types. We find associated candidate driver genes, and identify seven novel somatic mutations in CDH1, which is a well-known gastric cancer-associated gene. Three-dimensional structure analysis of the mutated E-cadherin protein suggests that these new somatic mutations could cause significant functional perturbations of critical calcium-binding sites in the EC1-2 junction. Chromosomal instability analysis shows that the MDM2 gene is amplified. After thorough structural analysis, a novel fusion gene TSC2-RNF216 is identified, which may simultaneously disrupt tumor-suppressive pathways and activate tumorigenesis.ConclusionsWe report the genomic profile of diffuse-type gastric cancers including new somatic variations, a novel fusion gene, and amplification and deletion of certain chromosomal regions that contain oncogenes and tumor suppressors.

The physical gelation behavior of high molecular weight (HMW) syndiotactic poly(vinyl alcohol) (S-PVA) was investigated in consideration of stereoregularity of the polymer. To precisely identify the effect of stereoregularity, syndiotactic diad (S-diad) contents of PVAs with the similar molecular weights were controlled to 61.5, 58.2, and 55.7%, respectively. The gel point (GP) of HMW S-PVA solution was determined by observing the frequency-independent loss tangent and the crossover between the relaxation exponents from the oscillatory shear experiment. The gelation process of HMW S-PVA solution with S-diad content over 58.2% was divided into two types with respect to the concentration of solution. The first type is the gelation that took place directly from sol to gel with a clear GP which was well coincident with the macroscopic gelation temperature (T gel). This is for the higher concentration regime. The second one is the gelation that occurred gradually accompanying the evolution of gel-like properties in sol state without a definite GP, which is for the lower concentration regime. The gel-like heterogeneity formed during the second type gelation might be related with the liquid-liquid phase separation. In contrast, HMW S-PVA solution with S-diad content of 55.7% followed only the first type gelation. The relaxation exponent of HMW S-PVA solution at GP decreased with concentration and had a lower value than the percolation value, 0.7. The higher fractal dimension indicates the structural compactness in the cross-linking system of HMW S-PVA. As compared with the other gelation system, lower gel stiffness was obtained, suggesting that the gelation of HMW S-PVA solution occurred without a serious crystallization.