Project description:To predict the progression risk of non-invasive gland-forming gastric neoplasms to invasive carcinoma, we assessed lineage continuity or discontinuity between the non-invasive and invasive neoplasms by applying hierarchical clustering analysis to the gene copy-number profiles of individual tumours.
Project description:To predict the progression risk of non-invasive gland-forming gastric neoplasms to invasive carcinoma, we assessed lineage continuity or discontinuity between the non-invasive and invasive neoplasms by applying hierarchical clustering analysis to the gene copy-number profiles of individual tumours. array-based Comparative Genomic Hybridization. Samples are including of 7 tumours of Vienna category 3, 12 tumours of Vienna category 4, 8 intramucosal cancers (Vienna category 5), 16 intramucosal lesions and 16 invasive parts (Vienna category 5); 40 reference for control, 19 control replicates
Project description:We tried progression risk prediction of individual gland-forming gastric cancers using genomic DNA copy number profile as a genetic lineage marker. The unsupervised clustering of DNA copy-number profiles of 107 gastric cancer samples, using large-sized (≥ 6 probes) genes, were divided into the loss-rich (A) and gain-rich (B) clusters. The T1/T2-4 ratio was significantly higher in cluster B and in cluster A (P < 0.0007). Small cancers (≤ 2 cm in diameter) were more frequent in cluster B than in cluster A. These 2 clusters were not linked to the frequency of metastasis but to the liability to progression from early to advanced stage; the cluster A may more readily become advanced than cluster B. Our approach suggested that the genetic lineages of early and advanced gland-forming gastric cancers are largely different; the eradication of small cluster B tumors (≤ 2 cm) by the present ESD indication may be valid, but not be effective for reduction of large, aggressive cluster A tumors.
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes