Project description:In human, the 39 coding HOX genes and 18 referenced non-coding antisense transcripts are arranged in four genomic clusters named HOXA, B, C, and D. This highly conserved family belongs to the homeobox class of genes that encode transcription factors required for normal development. Therefore, HOX gene deregulation might contribute to the development of many cancer types. Here, we study HOX gene deregulation in adult glioma, a common type of primary brain tumor. We performed extensive molecular analysis of tumor samples, classified according to their isocitrate dehydrogenase (IDH1) gene mutation status, and of glioma stem cells. We found widespread expression of sense and antisense HOX transcripts only in aggressive (IDHwt) glioma samples, although the four HOX clusters displayed DNA hypermethylation. Integrative analysis of expression-, DNA methylation- and histone modification signatures along the clusters revealed that HOX gene upregulation relies on canonical and alternative bivalent CpG island promoters that escape hypermethylation. H3K27me3 loss at these promoters emerges as the main cause of widespread HOX gene upregulation in IDHwt glioma cell lines and tumors. Our study provides the first comprehensive description of the epigenetic changes at HOX clusters and their contribution to the transcriptional changes observed in adult glioma. It also identified putative "master" HOX proteins that might contribute to the tumorigenic potential of glioma stem cells.
Project description:transcription profiling of human head and neck squamous cell carcinoma (HNSCC) samples vs. normal tonsil samples using a two-color reference design experimental setting. Used to identify differentially expressed genes in tumor/normal samples, and compare the result to that of the same samples using the self-self hybridization experimental setting. Keywords: tumor/normal comparison
Project description:Canine mammary gland tumors (CMTs) have been suggested as promising cancer models to human breast cancer due to their many biological and clinical similarities. Here, we collected 222 samples consist of 158 tumor samples and 64 matched normal samples of CMTs. Fresh tissue samples were transferred in to RNAlater, and refrigerated overnight at 4°C and then stored at -80°C. Total RNA was extracted from tissues using RNeasy mini kit. We aligned RNA-Seq raw data from 222 samples to canine reference genome CanFam3.1 using Tophat. We assembled transcript and calculated FPKM values using Cufflinks. All tumor samples were evaluated by histopathological characteristics including histopathological subtype, grade, and lymphatic invasion, and annotated with corresponding sequencing data. The histopathological classification and the histological grading system of CMTs were adopted from those of human breast cancer. In addition, immunohistochemical evaluation was performed in samples for estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. DISCLAIMER: Using this dataset became freely available on Jul 22, 2019. On the other hand, we are now preparing a key paper about comparative analysis of canine and human breast cancer based on this dataset. If you plan to submit a similar paper using this dataset before the main paper is published, please feel free to contact the submitter (swkim@yuhs.ac) to coordinate submission.
Project description:transcription profiling of human head and neck squamous cell carcinoma (HNSCC) samples vs. normal tonsil samples using a self-self hybridization experimental design on two-color arrays. Used to identify differentially expressed genes in tumor/normal samples, and compare the result to that of the same samples using the reference design experimental setting. Keywords: tumor/normal comparison