Project description:This is a continuation of the Chordoma Sequencing Project. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. RNA Sequencing/Methylation and SNP6 and an additional sequencing of three cancer cell lines will be added to this work.
Project description:Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents to treat chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Primary tumor from a sacral chordoma was xenografted into NOD/SCID/IL-2R γ-null mice. The xenograft is serially transplantable and was characterized by both gene expression analysis and whole genome SNP genotyping. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds using two established chordoma cell lines, U-CH1 and U-CH2B. The screen yielded several compounds that showed activity and two, sunitinib and bortezomib, were tested in the xenograft. Both agents slowed the growth of the xenograft tumor. Sensitivity to an inhibitor of IκB, as well as inhibition of an NF-κB gene expression signature demonstrated the importance of NF-κB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo preclinical drug testing. The copy number and allelic balance pattern of a novel human chordoma xenograft samples was determined with Illumina BeadChips.
Project description:The prognostic factors of skull base chordoma associated with outcomes of patients after surgical resection remain poorly defined. This project aimed to identify a novel prognostic factor for patients with skull base chordoma. Using a proteomics approach, we screened tumor biomarkersthat upregulated in the rapid-recurrence group of chordoma, narrowed down by bioinformatics analysis, and finally potential biomarker was chosen for validation by immunohistochemistry using tissue microarray.
Project description:Chromatin profiling of chordoma collected by the Broad chordoma target discovery project paired end ATAC-Seq profiling in the UCH2 and MUGCHOR chordoma cell lines
Project description:Duplication of T is a known familial susceptibility determinant for chordoma. TO determine if a similar genetic alteration occurs in the sporadic disease a high-resolution array-CGH (Agilent custom-designed arrayCGH chip) was used to interrogate the chr 6q27 locus for duplication of T. Twenty two samples of chordoma and reference genomic DNA were hybridised to the chip including a positive control from a chordoma cell line.
Project description:Chordoma is a rare, resistant bone tumor thought to be arised from remnants of embryonic notochord. Cancer stem cells (CSCs) are associated with tumorigenesis, recurrence and resistance in cancers. Here, we used miRNA and mRNA transcriptome analysis to discover novel genes and networks in chordoma CSCs
Project description:Chordoma is a rare, resistant bone tumor thought to be arised from remnants of embryonic notochord. Cancer stem cells (CSCs) are associated with tumorigenesis, recurrence and resistance in cancers. Here, we used miRNA and mRNA transcriptome analysis to discover novel genes and networks in chordoma Cancer Stem Cells
Project description:Chordoma is a rare malignant tumor thought to originate from embryonic notochord. However, no molecular comparison of chordoma and notochord has been performed to date, leaving the identities of dysregulated pathways unclear. Absence of a molecular description of a control tissue clouds our understanding of chordoma. Thus, we conducted an unbiased comparison of chordoma and notochord using gene expression profiling to clarify chordoma’s tissue of origin and identify novel drug targets
Project description:Chordoma is a rare malignant tumor thought to originate from embryonic notochord. However, no molecular comparison of chordoma and notochord has been performed to date, leaving the identities of dysregulated pathways unclear. Absence of a molecular description of a control tissue clouds our understanding of chordoma. Thus, we conducted an unbiased comparison of chordoma and notochord using gene expression profiling to clarify chordoma’s tissue of origin and identify novel drug targets