Whole Genome Sequencing for Metastatic Mutational Burden in Extraskeletal Myxoid Chondrosarcoma
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PROVIDER: PRJNA974550 | ENA |
REPOSITORIES: ENA
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Project description:Whole Genome Sequencing for Metastatic Mutational Burden in Extraskeletal Myxoid Chondrosarcoma
| PRJNA974549 | ENA
Project description:Extraskeletal myxoid chondrosarcoma (EMC) is an ultra-rare cancer that makes up less than 3% of all soft tissue sarcomas. It most often arises in the soft tissues of the proximal limbs and has a higher incidence in males. Though EMC has a good prognosis, it has an indolent course with high rates of local recurrence as well as metastasis to the lungs. EMC is characterized in 70% of cases by an EWS1-NR4A3 translocation, leading to constitutive expression of NR4A3. Structural variants (SVs) in EMC, especially large-scale genomic alterations, have not been well studied and studies are severely limited by sample size. In this study, we describe Whole Genome Sequencing (WGS) of a rare case of matched EMC primary tumor, lung metastasis, and pelvic metastasis to identify genomic alterations. We examined somatic variants, copy number variants (CNVs), and larger scale SVs such as translocations and breakend points. While the primary tumor and lung metastasis had similar somatic variations and CNVs, the pelvic metastasis had more unique SVs with especially increased mutational burden of SVs in chromosome 2. This suggests that different molecular drivers appear in more advanced, relapsing EMC compared with the primary tumor and early lung metastasis. Genomic studies such as ours may identify novel molecular complexities in rare cancers that may be leveraged for therapeutic strategies and precision medicine.
| S-EPMC11285543 | biostudies-literature
Project description:Abstract: Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42,000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that NMB was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Computed
2006-03-14 | E-GEOD-4303 | biostudies-arrayexpress
Project description:Abstract: Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42,000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that NMB was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Keywords: all_pairs
2006-03-15 | GSE4303 | GEO
Project description:Characterization of tumor mutational burden in LKB1 mutant lung tumors
| PRJNA564852 | ENA
Project description:Inactivating mutations in LKB1/STK11 are present in ~20% of non-small cell lung cancers (NSCLC) and portend poor response to anti-PD-1 immunotherapy in patients and genetically engineered mouse model (GEMMs). Here, we sought to uncover the basis for immunotherapy resistance of these tumors and to define strategies that overcome this barrier. Whereas high tumor mutational burden (TMB) often correlates with response to anti-PD1 treatment, we found that LKB1-deficient NSCLCs from non-smokers and GEMMs exhibited striking elevations in nonsynonymous mutations compared to LKB1 wildtype tumors. Correspondingly, LKB1 mutant NSCLC cell lines showed defects in both replication dependent and independent double-strand DNA break (DSB) repair, which were reversed upon LKB1 re-expression.
2021-03-17 | GSE137244 | GEO
Project description:The aim of this project is to use high-throughput transcriptomic approach to decipher the tumor mutational burden (TMB) of two cancer cell lines, MBT2 (urothelial) and LM8 (osteosarcoma), syngeneic of the C3H/HeN mouse strain, and to compare them as biomarker of immunogenicity (Rizvi NA et al. Science, 2015, Sha D et al. Cancer Discovery, 2020).
2024-05-31 | GSE224642 | GEO
Project description:Round cell component is a resk factor associated with metastasis and poor prognosis in myxoid liposarcoma. To identify microRNAs which play a role in the malignancy of round cell component, we performed microRNA microarray analysis and compared the miRNA expression profilings between myxoid and round cell component.
2017-02-09 | GSE73348 | GEO
Project description:In order to identify new key molecules in the pathogenesis of myxoid liposarcoma, we performed comparative gene expression profiling in myxoid liposarcoma and fat tissue samples.
2014-10-28 | GSE62747 | GEO
Project description:miR-135b expression is higher in myxoid liposarcoma cell lines than in adipose-derived mesenchymal cell line, as well as in myxoid liposarcoma tumors than in adjacent normal prostate tissues.To further investigate the molecular mechanisms regulated by miR-135b, we performed mRNA microarray analysis of cell cultures from myxoid liposarcoma cell line after transfections with miR-135b mimic or negative control.
2017-02-09 | GSE73347 | GEO