Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA198519 | ENA |
REPOSITORIES: ENA
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Project description:Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are frequently driven by recurrent gene rearrangements. In conventional low-grade ESSs, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1 chimeric fusions have been reported in > 50% of cases. The recently described t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and conventional cytogenetics, we identified MBTD1 (Malignant Brain Tumor Domain-containing 1) and CXorf67 (Chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using RT-PCR followed by Sanger sequencing. A specific FISH assay to be used on paraffin tissues was developed to detect the novel t(X;17) translocation, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 14 uterine stromal tumours [9 ESSs and 5 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of 3 ESSs with YWHAE- and 4 classical ESSs with JAZF1-rearrangements, and 4 UESs without known gene rearrangements, indicated clustering of tumours with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESSs. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes. Genomic DNA extracted from 2 low-grade ESS frozen tumor samples; Agilent CGH+SNP 4x180K array. Reference female DNA supplied with the SureTag Complete DNA Labeling Kit was used for the aCGH experiments.
2015-03-31 | E-GEOD-46284 | biostudies-arrayexpress
Project description:Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are frequently driven by recurrent gene rearrangements. In conventional low-grade ESSs, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1 chimeric fusions have been reported in >50% of cases. The recently described t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and conventional cytogenetics, we identified MBTD1 (Malignant Brain Tumor Domain-containing 1) and CXorf67 (Chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using RT-PCR followed by Sanger sequencing. A specific FISH assay to be used on paraffin tissues was developed to detect the novel t(X;17) translocation, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 14 uterine stromal tumours [9 ESSs and 5 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of 3 ESSs with YWHAE- and 4 classical ESSs with JAZF1-rearrangements, and 4 UESs without known gene rearrangements, indicated clustering of tumours with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESSs. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes. Total RNA was extracted from 11 frozen tumor samples from 4 low-grade ESS cases, 4 UES cases and 3 high-grade ESS cases; Agilent One-Color technology.
2015-03-31 | E-GEOD-45783 | biostudies-arrayexpress
Project description:Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are frequently driven by recurrent gene rearrangements. In conventional low-grade ESSs, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1 chimeric fusions have been reported in > 50% of cases. The recently described t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and conventional cytogenetics, we identified MBTD1 (Malignant Brain Tumor Domain-containing 1) and CXorf67 (Chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using RT-PCR followed by Sanger sequencing. A specific FISH assay to be used on paraffin tissues was developed to detect the novel t(X;17) translocation, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 14 uterine stromal tumours [9 ESSs and 5 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of 3 ESSs with YWHAE- and 4 classical ESSs with JAZF1-rearrangements, and 4 UESs without known gene rearrangements, indicated clustering of tumours with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESSs. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes.
2015-03-31 | GSE46284 | GEO
Project description:Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are frequently driven by recurrent gene rearrangements. In conventional low-grade ESSs, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1 chimeric fusions have been reported in >50% of cases. The recently described t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and conventional cytogenetics, we identified MBTD1 (Malignant Brain Tumor Domain-containing 1) and CXorf67 (Chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using RT-PCR followed by Sanger sequencing. A specific FISH assay to be used on paraffin tissues was developed to detect the novel t(X;17) translocation, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 14 uterine stromal tumours [9 ESSs and 5 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of 3 ESSs with YWHAE- and 4 classical ESSs with JAZF1-rearrangements, and 4 UESs without known gene rearrangements, indicated clustering of tumours with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESSs. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes.
2015-03-31 | GSE45783 | GEO
Project description:Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade endometrial stromal sarcoma
| PRJNA198518 | ENA
Project description:Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade endometrial stromal sarcoma (expression)
| PRJNA196324 | ENA
Project description:Dysregulation of Polycomb Repressive Complex 2 (PRC2) function is a common feature of many cancer types, including both solid and hematological malignancies. A number of chromosomal translocations involving Polycomb group proteins have been identified, however, the molecular function of these fusion proteins remains largely unexplored. Here we characterize two endometrial stromal sarcoma (ESS) associated fusion proteins: JAZF1-SUZ12 and MBTD1- CXORF67. We identify JAZF1 as a previously unreported subunit of the NuA4 complex, which when fused to SUZ12 creates a bridge between the NuA4 and PRC2 complexes. Intriguingly, the MBTD1-CXORF67 fusion binds to PRC2 and leads to strongly reduced levels of the PRC2 catalytic products H3K27me2/3. We demonstrate that this inhibitory function is mediated by the CXORF67 half of the fusion protein. Because of this striking property, we propose a new gene name: CATACOMB (CATalytic Antagosnist of polyCOMB, official gene name: EZHIP). We map CATACOMB’s inhibitory function to a short highly conserved region and identify a single methionine residue essential for diminution of H3K27me2/3 levels. Remarkably, the amino acid sequence surrounding this critical methionine resembles that of the oncogenic histone H3 lysine-27-to-methionine (H3K27M) mutation found in high grade pediatric gliomas. Finally, we show CATACOMB expression is silenced through DNA methylation and upon treatment with DNA demethylating agents, CATACOMB is expressed, binds to PRC2 and antagonizes its catalytic activity. In conclusion, we have identified an endogenous inducible gene, CATACOMB, that it’s expression can regulate catalytic activity of PRC2 and propose that such mechanism of regulation of histone modifications through the expression of antagonistic subunits may also exist for Trithorax/COMPASS family and other histone modifying enzyme complexes.
2019-06-03 | GSE131626 | GEO
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
2022-02-18 | GSE196754 | GEO
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
2020-12-03 | GSE162543 | GEO
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
2020-11-25 | GSE162118 | GEO