Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Karolin Nord

PROVIDER: E-GEOD-38104 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.

Nord Karolin H KH Paulsson Kajsa K Veerla Srinivas S Wejde Johan J Brosjö Otte O Mandahl Nils N Mertens Fredrik F

Neoplasia (New York, N.Y.) 20120901 9

Inflammatory leiomyosarcoma (ILMS) is a soft tissue tumor that morphologically resembles conventional leiomyosarcoma (LMS) admixed with a prominent inflammatory infiltrate. Genetic data on ILMS are still limited but have suggested that this entity is characterized by hyperhaploidy (24-34 chromosomes). This low chromosome number is otherwise uncommon in neoplasia and has been found only in 0.2% to 0.3% of cytogenetically investigated tumors. Here, three ILMS were investigated using cytogenetic, s ...[more]

PMID: 23019412

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Project description:Inflammatory leiomyosarcoma (ILMS) is a soft tissue tumor that morphologically resembles conventional leiomyosarcoma (LMS) admixed with a prominent inflammatory infiltrate. Genetic data on ILMS are still limited but have suggested that this entity is characterized by hyperhaploidy (24-34 chromosomes). This low chromosome number is otherwise uncommon in neoplasia and has been found only in 0.2-0.3% of cytogenetically investigated tumors. Here, three ILMS were investigated using cytogenetic, SNP array and global gene expression analyses. All cases displayed a hyperhaploid origin. Combined with previously reported cases, hyperhaploidy has been found in six of seven cytogenetically investigated ILMS. The copy number distribution of individual chromosomes is clearly nonrandom; the hyperhaploid clones of all six cases displayed disomy for chromosomes 5 and 20, and two copies of chromosomes 18, 21 and 22 were also common. All chromosomes identified as disomic showed a biparental origin by SNP array analysis; whether this is of pathogenetic importance is not known. Compared with conventional LMS, ILMS had a distinct gene expression signature. Furthermore, the number of chromosome copies correlated well with gene expression levels, a finding which has not previously been reported for hyperhaploid tumors. Genes on disomic chromosomes showed higher expression levels in ILMS compared to LMS and disomic chromosomes showed higher average gene expression levels than monosomic chromosomes. Taken together, our findings suggest that disomy for some chromosomes, notably 5 and 20, as well as distorted gene expression balance achieved through massive loss of other chromosomes are essential for the development of ILMS. Tumor DNA was hybridized onto Illumina Human CNV370-Quad v3_C (case 1) and Illumina Human CNV370 v1_C (cases 2 and 3) BeadChips, containing ~370,000 markers, following standard protocols supplied by the manufacturer (Illumina). Data analysis was performed using the GenomeStudio software (Illumina), detecting imbalances by visual inspection.

Project description:Background: Ameloblast differentiation is the most critical stepwise process in amelogenesis and controlled by a precisely molecules synergistically. To better understand the molecular events defining cell differentiation between preameloblasts and secretory ameloblasts during amelogenesis, a more precise identification of molecules and signaling networks would shed light on the mechanisms governing enamel formation and help lay a foundation for enamel regeneration. Results: Gene expression profiles of human preameloblast and secretory ameloblast cells were obtained using human genome microarrays. From a total of 28,869 analyzed transcripts, 923 differentially expressed genes (DEGs) with FDR<0.01 and Fold-change > 2 were obtained. Among them, more than twice DEGs were found enriched in PAB (n = 647) compared with SAB (n = 276). Notably, 38 genes were identified significantly differentially expressed between PAB and SAB (Fold Change > 8). Comparison of transcriptional profiles of PAB and SAB together with KEGG pathway analysis revealed genes enrichment in PAB were chiefly involved in cell cycle control, DNA damage repair and apoptosis, while genes related to cell adhesion and extracellular matrix had elevated expression level in SAB. Two co-expression modules were further identified significantly associated with the ameloblast differentiation process by weighted gene co-expression network analysis (WGCNA).These gene networks seem to contribute to cell adhesion, tissue development, cell signaling and division. Furthermore, the co-expression associations of RunX2 and BMP8A were also observed in these modules. Conclusions: In this study, we uncovered that the differentiation from PAB to SAB may rely on a highly regulated network of interactions between conserved signal transduction pathways, including members of BMP/TGF-β, Notch, MAPK pathways to coordinate all aspects of ameloblast in intracellular processes and their social contexts. Specifically, expression of genes associated with cell cycle control, DNA damage repair, and apoptosis pathways regulates pre-ameloblast maturation during tooth development. And the SAB cells are regulated by several signaling pathways controlling enamel matrix proteins secretion and cell adhesion, which are critical for enamel formation and cell-cell interactions. Apart from showing the transcriptional patterns of PAB and SAB, the application of bioinformatic analysis also explored the potential key genes and gene-associations in ameloblast differentiation. These findings will aid in the design of new strategies to promote ameloblast functional differentiation in the regeneration and tissue engineering of teeth. Human tooth buds (18-22 weeks) were obtained from fetal cadaver tissue within 3 hours after legal abortion. Teeth were dissected from the mandibles under a laminar flow hood, embedded in OCT compound, and cryosectioned at 10-μm thickness. These sections were used for laser capture microdissection (LCM). In total of 3 pre-ameloblasts and 3 secretory ameloblasts pooled samples were used for RNA extraction and hybridization on Affymetrix microarray.

Dataset Information

Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma

Publications

Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.

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