Similar Datasets
Project description:Near Haploidization is a Genomic Hallmark of Giant Cell Glioblastoma
| PRJNA662325 | ENA
Project description:BackgroundGiant cell glioblastoma (gcGBM) is a rare histologic subtype of glioblastoma characterized by numerous bizarre multinucleate giant cells and increased reticulin deposition. Compared with conventional isocitrate dehydrogenase (IDH)-wildtype glioblastomas, gcGBMs typically occur in younger patients and are generally associated with an improved prognosis. Although prior studies of gcGBMs have shown enrichment of genetic events, such as TP53 alterations, no defining aberrations have been identified. The aim of this study was to evaluate the genomic profile of gcGBMs to facilitate more accurate diagnosis and prognostication for this entity.MethodsThrough a multi-institutional collaborative effort, we characterized 10 gcGBMs by chromosome studies, single nucleotide polymorphism microarray analysis, and targeted next-generation sequencing. These tumors were subsequently compared to the genomic and epigenomic profile of glioblastomas described in The Cancer Genome Atlas (TCGA) dataset.ResultsOur analysis identified a specific pattern of genome-wide massive loss of heterozygosity (LOH) driven by near haploidization in a subset of glioblastomas with giant cell histology. We compared the genomic signature of these tumors against that of all glioblastomas in the TCGA dataset (n = 367) and confirmed that our cohort of gcGBMs demonstrated a significantly different genomic profile. Integrated genomic and histologic review of the TCGA cohort identified 3 additional gcGBMs with a near haploid genomic profile.ConclusionsMassive LOH driven by haploidization represents a defining molecular hallmark of a subtype of gcGBM. This unusual mechanism of tumorigenesis provides a diagnostic genomic hallmark to evaluate in future cases, may explain reported differences in survival, and suggests new therapeutic vulnerabilities.
| S-EPMC7764500 | biostudies-literature
Project description:Giant cell ependymoma (GCE), a rare ependymoma subtype, was only recently recognised as a separate diagnostic entity with variations both in malignant potential and in course of disease. The pathogenetic mechanisms behind ependymomas remain unknown. Only one karyotyped GCE has so far been reported. We present the first genomic characterisation of a supratentorial GCE using G-band karyotyping, DNA ploidy analysis and array comparative genomic hybridisation (aCGH). The G-banded karyotype was hypodiploid with multiple monosomies, a feature present also in the previously published case and, hence, probably characteristic of these tumours. We could also analyse cytogenetically a subsequent recurrent tumour, phenotypically an anaplastic ependymoma, but exhibiting a pattern of monosomies largely similar to that found in the primary tumour, allowing a first insight into the genetic events involved also in disease progression. 2 tumour samples analysed with the control DNA (supplied by Agilent)
2010-08-30 | E-GEOD-23065 | biostudies-arrayexpress
Project description:The giant panda (Ailuropoda melanoleuca) stands as a flagship and umbrella species, symbolizing global biodiversity. While traditional assisted reproductive technology faces constraints in safeguarding the genetic diversity of giant pandas and bolstering the population size of giant pandas, induced pluripotent stem cells (iPSCs) known for their capacity to differentiate into diverse cells types, including germ cells, present a transformative potential for conservation of endangered animals. In our study, we isolated primary fibroblast cells from an individual giant panda and successfully generated giant panda induced pluripotent stem cells (GPiPSCs) through a non-integrating episomal vectors reprogramming method. Characterization of these GPiPSCs revealed their state of primed pluripotency and demonstrated their potential for differentiation. Furthermore, we innovatively formulated a species-specific chemically defined FACL medium and unraveled the intricate signaling pathway networks responsible for maintaining the pluripotency and fostering cell proliferation of GPiPSCs. This study provides key insights into rare species iPSCs, offering materials for panda characteristics research and laying the groundwork for in vitro giant panda gamete generation, potentially aiding endangered species conservation.
2024-09-25 | GSE250292 | GEO
Project description:Large and giant congenital melanocytic nevi (CMN) are rare melanocytic lesions mostly caused by post-zygotic acquisition of NRAS alteration. However, large/giant CMN may exhibit phenotypic differences among distinct areas patients and in addition, patients differ in features such as presence of multiple CMN or Spilus-like lesions. Overall, 50 fresh-frozen biopsies corresponding to 37 phenotypically characterized areas of large/giant CMNs, 9 satellite lesions, 1 acquired nevus and 3 healthy skin biopsies were analyzed by a multigene panel and RNA sequencing (RNA-seq). Mutational screening showed mutations in 76.2% of large/giant CMN. NRAS mutation was found in 57.1% of cases, and mutations in other genes such as BRAF, KRAS, APC and MET were detected in 14.3% of patients. RNA-seq revealed the fusion transcript ZEB2-ALK and SOX5-RAF1 in large/giant CMN from two patients without point mutations. Both alterations were not detected in unaffected skin and were detected in different affected skin. These findings suggest that large/giant CMN may result from distinct molecular events in addition to NRAS mutations including point mutations and fusions transcripts.
2019-10-24 | GSE120597 | GEO
Project description:Giant cell ependymoma (GCE), a rare ependymoma subtype, was only recently recognised as a separate diagnostic entity with variations both in malignant potential and in course of disease. The pathogenetic mechanisms behind ependymomas remain unknown. Only one karyotyped GCE has so far been reported. We present the first genomic characterisation of a supratentorial GCE using G-band karyotyping, DNA ploidy analysis and array comparative genomic hybridisation (aCGH). The G-banded karyotype was hypodiploid with multiple monosomies, a feature present also in the previously published case and, hence, probably characteristic of these tumours. We could also analyse cytogenetically a subsequent recurrent tumour, phenotypically an anaplastic ependymoma, but exhibiting a pattern of monosomies largely similar to that found in the primary tumour, allowing a first insight into the genetic events involved also in disease progression.
2010-08-30 | GSE23065 | GEO
Project description:We characterized the mouse trophoblast giant cell epigenome and gene expression profiles. We then compared these data to our data on underrepresentation in the polyploid trophoblast giant cells. We profiled 5 histone modifications (+ chromatin input) using ChIP-Seq, and digital expression profiles (3' RNA-Seq) for trophoblast giant cells derived from mouse. Furthermore, we profiled digital expression profiles (3' RNA-Seq) for in vivo trophoblast giant cells samples from e9.5 wildtype mouse trophoblast giant cells. We found that underrepresented domains in trophoblast giant cells are enriched for repressive marks and anti-correlate with active marks and transcription.
2014-05-29 | E-GEOD-50561 | biostudies-arrayexpress
Project description:We characterized the mouse trophoblast giant cell epigenome and gene expression profiles. We then compared these data to our data on underrepresentation in the polyploid trophoblast giant cells.
2014-05-29 | GSE50561 | GEO
Project description:Giant cell granulomas of the jaws often occur sporadically as single central or peripheral lesions. They are characterized by KRAS, FGFR1, or TRPV4 somatic mutations, the latter occurring exclusively in the central form. Less commonly, multiple giant cell lesions can develop in the context of syndromes such as cherubism, which is an autosomal dominant bone disease. Morphologically, giant cell granulomas can closely resemble other giant cell-rich lesions such as non-ossifying fibroma and aneurysmal bone cyst, and to a minor extent giant cell tumour of bone and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and, recently, DNA methylation profile has been shown to be clinically useful for the diagnosis of other tumour types, including brain tumours as well as bone and soft tissue sarcomas. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic giant cell granulomas of the jaws and cherubism to test whether DNA methylation patterns can help to distinguish these entities. Additionally, we further compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. Our results showed that central and peripheral sporadic giant cell granulomas of the jaws and cherubism share a related DNA methylation pattern with that of peripheral sporadic giant cell granulomas and cherubism appearing slightly distinct, while central sporadic giant cell granulomas show overlap with both of the former. Non-ossifying fibroma, aneurysmal bone cyst, giant cell tumour of bone, and chondroblastoma, on the other hand, have distinct methylation patterns. Therefore, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions of the jaws. Conversely, it could discriminate sporadic giant cell granulomas from their giant cell-rich mimics.
2023-10-18 | GSE218252 | GEO