Project description:Spontaneously occurring canine mammary cancer represents an excellent model of human breast cancer, but is greatly understudied. To better use this valuable resource, we performed whole-genome sequencing, whole-exome sequencing, RNA-seq, and/or high-density arrays on twelve canine mammary cancer cases, including seven simple carcinomas and four complex carcinomas. Canine simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many of which faithfully recapitulate key features of human breast cancer. Canine complex carcinomas, which are characterized by proliferation of both luminal and myoepithelial cells and are rare in human breast cancer, seem to lack genomic abnormalities. Instead, these tumors have about 35 chromatin-modification genes downregulated and are abnormally enriched with active histone modification H4-acetylation, whereas aberrantly depleted with repressive histone modification H3K9me3. Our findings indicate the likelihood that canine simple carcinomas arise from genomic aberrations, whereas complex carcinomas originate from epigenomic alterations, reinforcing their unique value. Canine complex carcinomas offer an ideal system to study myoepithelial cells, the second major cell lineage of the mammary gland. Canine simple carcinomas, which faithfully represent human breast carcinomas at the molecular level, provide indispensable models for basic and translational breast cancer research.
Project description:To identify the therapeutic targets in a treatment-refractroy cancer patient, we performed single-cell RNA sequencing for 3,115 cells from primary bladder cancer (BC159-T#3) and patient-derived xenografts (BC159-T#3-PDX-vehicle and BC159-T#3-PDX-tipifarnib). Matched time-series bulk tumor tissues were also sequenced using whole exome target probe (WES) and whole transcriptome target probe (WTS).
Project description:To identify the therapeutic targets in a treatment-refractory cancer patient, we performed single-cell RNA sequencing for 3,115 cells from primary bladder cancer (BC159-T#3) and patient-derived xenografts (BC159-T#3-PDX-vehicle and BC159-T#3-PDX-tipifarnib). Matched time-series bulk tumor tissues were also sequenced using whole exome target probe (WES) and whole transcriptome target probe (WTS).
Project description:Cancer stem cells (CSCs) are fundamental to bladder cancer progression and the cyclooxygenase-2 (COX-2) pathway has a pro-tumorigenic role in CSC function. Naturally occurring bladder cancer in dogs has the potential to be a natural model of the human disease. Here, we used canine specific microarrays to determine changes in global gene expression of canine bladder cancer cells (the K9TCC cell line) and bladder cancer stem cells isolated from the K9TCC cell line after treatment with the selective COX-2 inhibitor mavacoxib or a COX-2 siRNA.
2022-07-20 | GSE183793 | GEO
Project description:Canine Cancer Cell Line Whole Exome Sequencing
Project description:Agilent whole exome hybridisation capture was performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products.
Project description:ARID1A, a subunit of SWI/SNF chromatin remodeling complex. SWI/SNF complex can regulate expression of genes involved in vital biological processes such as cell cycle, DNA damage repair and development. ARID1A is known to have high mutation rate in human cancers including bladder cancer, leading to its loss of function. Publicly available whole exome sequencing data for muscle invasive and non-muscle invasive bladder cancers, show fraction of tumors with truncated ARID1A. Thus identifying therapeutic strategies for ARID1A mutant cancers is of high importance. EZH2, a histone methyltransferase is known to over-express and play pivotal role in aggressive bladder cancer. Our preliminary studies show that treatment of EZH2 inhibitor (GSK126) on ARID1A mutant bladder cancer cells significantly reduced cancer cell viability, invasion and colony formation relative to wild type ARID1A containing cells. Here, we performed microarray experiments to assess the effect of EZH2 inhibitor on global transcriptome of both ARID1A mutant and wild type bladder cancer cell line.
Project description:Purpose: There are three goals of this study: 1. To compare the genomic, exome and chromatin accessiblity profiles of the specific engineered fallopian tube cells of high-grade serous tubo-ovarian cancer (HGSC) models (this study) using whole-exome, whole-genome and ATAC-seq sequencing. Methods: For whole-exome analysis, genomic DNA was extracted from the cell lines mentioned below. Conclusions: We conclude that whole-exome, whole-genome and ATAC-seq characterization would expedite genetic network analyses and permit the dissection of complex biological functions.