Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways.

Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics. The mucin family of genes, MUC6, MUC12, and MUC4, were found to be highly mutated in the OS patients. Results revealed the enrichment of molecular pathways including Wnt signaling, Calcium signaling, and PI3K-Akt signaling in the OS tumors. Survival analyses showed that the expression levels of several genes such as RAMP1, CRIP1, CORT, CHST13, and DDX60L, miRNAs and lncRNAs were associated with survival of OS patients. Molecular subtyping using Cluster-Of-Clusters Analysis (COCA) for mRNA, lncRNA, and miRNA expression; DNA methylation; and mutation data from the TARGET dataset revealed two distinct molecular subtypes, each with a distinctive gene expression profile. Between the two subtypes, three upregulated genes, POP4, HEY1, CERKL, and seven downregulated genes, CEACAM1, ABLIM1, LTBP2, ISLR, LRRC32, PTPRF, and GPX3, associated with OS metastasis were found to be differentially regulated. Thus, the molecular subtyping results provide a strong basis for classification of OS patients that could be used to develop better prognostic treatment strategies.

SSR repeat dynamics in mitochondrial genomes of five domestic animal species.

SSR (simple sequence repeats) are ubiquitously abundant in genomes. In organellar mitochondrial genome of animals, its distribution, size dynamics and effectiveness for phylogenetic relationship have not been understood. Present investigation reveals organisation of SSR in genic and intergenic region, its length and repeat motif dynamics, extent of conservation of flanking regions, appropriateness of these SSR data in establishing phylogenetic relationship. Contrary to eukaryotic nuclear abundance of SSR in non-coding region, we found abundance in coding region. Like nuclear SSR, most hyper mutable repeats were found in non coding region having di nucleotide motifs of mitochondrial genome but contrary to human having high mutable tetra repeats in case of mitochondrial genomes this was found to be with tri-motif repeats. SSR of mitochondrial genomes also show cyclical expansion and shrinkage in pattern of SHM (simple harmonic motion) with respect to time its non- linear thus not appropriate for phylogenetic analysis though the flanking regions of these SSR also conserved like nuclear SSR.