Implication of Nos2 inactivation on the transcriptome of developing cerebellum and Ptch1+/- medulloblastomas (mRNA)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE29192 | GEO | 2011/12/01
SECONDARY ACCESSION(S): PRJNA142989
REPOSITORIES: GEO
Similar Datasets
Project description:The Ptch1+/- strain constitues an established mouse model for the Shh-driven type of medulloblastoma. Combined Ptch1+/- Nos2-/- mice show a two-fold increased incidence for this tumor. Here, the impact of Nos2 inactivation on medulloblastoma development was investigated by gene expression profiling of tumor samples as well as healthy cerebellum at different ages and genotypes. Medulloblastoma samples from three Ptch1+/- and six combined Ptch1+/- Nos2-/- mice were analyzed. Healthy cerebellum taken from mice at postnatal day nine, six weeks after birth, and about 1 year of age were analyzed for wildtype animals and the genotypes Ptch1+/-, Ptch1+/- Nos2-/-, and Nos2-/-. The cerebellar developmental stages at six weeks and one year were measured in three biological replicates, while samples taken at postnatal day six consisted of pooled individual specimen. These were measured in three replicates being amplified and labelled in separate reactions. All samples were subjected to two-color hybridizations against Universal Reference RNA (Stratagene) with color-switch experiments yielding two technical replicates, respectively.
2011-12-01 | E-GEOD-29192 | biostudies-arrayexpress
Project description:The Ptch1+/- strain constitues an established mouse model for the Shh-driven type of medulloblastoma. Combined Ptch1+/- Nos2-/- mice show a two-fold increased incidence for this tumor. Here, the impact of Nos2 inactivation on copy number alterations during medulloblastoma development was investigated by array-based comparative genomic hybridization (arrayCGH) of tumor samples from both genotypes. Medulloblastoma samples from five Ptch1+/- and seven compound Ptch1+/- Nos2-/- mice were analyzed. Cy5-labeled tumor DNA was combined with corresponding Cy3-labeled reference healthy wildtype genomic DNA to receive either sex-matched sample pairs or pairs of different gender for internal negative or positive control.
2011-12-01 | E-GEOD-29199 | biostudies-arrayexpress
Project description:The Ptch1+/- strain constitues an established mouse model for the Shh-driven type of medulloblastoma. Combined Ptch1+/- Nos2-/- mice show a two-fold increased incidence for this tumor. Here, the impact of Nos2 inactivation on copy number alterations during medulloblastoma development was investigated by array-based comparative genomic hybridization (arrayCGH) of tumor samples from both genotypes.
2011-12-01 | GSE29199 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE29192: Implication of Nos2 inactivation on the transcriptome of developing cerebellum and Ptch1+/- medulloblastomas (mRNA) GSE29199: Implication of Nos2 inactivation on genomic changes in Ptch1+/- medulloblastomas (array-CGH) Refer to individual Series
2011-12-01 | E-GEOD-29201 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-12-01 | GSE29201 | GEO
Project description:Genomic radiation signature illuminates low-dose effects with sharply reflected transcriptome in Ptch1-deficient medulloblastomas. Cancer risks of low-dose radiation are of great concern especially in relation to rapidly increasing medical exposures; however, their accurate assessments cope with many challenges and difficulties, partly due to the inability to distinguish radiation-induced tumors from spontaneous ones. Here, we analyzed the dose-dependent effect of radiation on medulloblastoma development in Ptch1 heterozygous mice on C3B6F1 background. The incidence and latency of medulloblastoma increased and shortened with increasing radiation dose, respectively. Amazingly, radiation contributed to tumorigenesis even at 50 mGy and 100% of mice got medulloblastoma with 1.5 Gy. Loss of heterozygosity (LOH) analysis on a total of 164 tumors indicated that spontaneous tumors showed LOH in broad regions on chromosome 13, including Ptch1 and distally-extending telomeric portion (S-type). In contrast, tumors developed after 3 Gy irradiation exhibited interstitial losses around Ptch1 (R-type). A clear dose-dependent increase in the proportion of R-type tumor at intermediate doses suggested R-type to be a reliable radiation signature. Array-CGH analysis indicated the R-type-specific copy-number reduction around Ptch1 and LOH-type-independent frequent gains of whole chromosome 6. Integrated expression microarray analysis indicated that expression levels of many genes within the altered genomic regions faithfully reflected the genomic copy-number changes. Furthermore, it was also suggested that these expression changes in turn influenced on many other genes, such as Tgfb2 and Tgfb3, on widespread genomic regions. This is the first demonstration that radiation-induced tumors developed after low-dose irradiation can be characterized quite precisely by interstitial deletion of Ptch1 and by associated gene expression profile. Gene expression in 3 normal cerebellum tissues and 12 medulloblastomas was measured.
2010-07-14 | E-GEOD-19360 | biostudies-arrayexpress
Project description:Genomic radiation signature illuminates low-dose effects with sharply reflected transcriptome in Ptch1-deficient medulloblastomas. Cancer risks of low-dose radiation are of great concern especially in relation to rapidly increasing medical exposures; however, their accurate assessments cope with many challenges and difficulties, partly due to the inability to distinguish radiation-induced tumors from spontaneous ones. Here, we analyzed the dose-dependent effect of radiation on medulloblastoma development in Ptch1 heterozygous mice on C3B6F1 background. The incidence and latency of medulloblastoma increased and shortened with increasing radiation dose, respectively. Amazingly, radiation contributed to tumorigenesis even at 50 mGy and 100% of mice got medulloblastoma with 1.5 Gy. Loss of heterozygosity (LOH) analysis on a total of 164 tumors indicated that spontaneous tumors showed LOH in broad regions on chromosome 13, including Ptch1 and distally-extending telomeric portion (S-type). In contrast, tumors developed after 3 Gy irradiation exhibited interstitial losses around Ptch1 (R-type). A clear dose-dependent increase in the proportion of R-type tumor at intermediate doses suggested R-type to be a reliable radiation signature. Array-CGH analysis indicated the R-type-specific copy-number reduction around Ptch1 and LOH-type-independent frequent gains of whole chromosome 6. Integrated expression microarray analysis indicated that expression levels of many genes within the altered genomic regions faithfully reflected the genomic copy-number changes. Furthermore, it was also suggested that these expression changes in turn influenced on many other genes, such as Tgfb2 and Tgfb3, on widespread genomic regions. This is the first demonstration that radiation-induced tumors developed after low-dose irradiation can be characterized quite precisely by interstitial deletion of Ptch1 and by associated gene expression profile.
2010-07-14 | GSE19360 | GEO
Project description:Genomic radiation signature illuminates low-dose effects with sharply reflected transcriptome in Ptch1-deficient medulloblastomas. Cancer risks of low-dose radiation are of great concern especially in relation to rapidly increasing medical exposures; however, their accurate assessments cope with many challenges and difficulties, partly due to the inability to distinguish radiation-induced tumors from spontaneous ones. Here, we analyzed the dose-dependent effect of radiation on medulloblastoma development in Ptch1 heterozygous mice on C3B6F1 background. The incidence and latency of medulloblastoma increased and shortened with increasing radiation dose, respectively. Amazingly, radiation contributed to tumorigenesis even at 50 mGy and 100% of mice got medulloblastoma with 1.5 Gy. Loss of heterozygosity (LOH) analysis on a total of 164 tumors indicated that spontaneous tumors showed LOH in broad regions on chromosome 13, including Ptch1 and distally-extending telomeric portion (S-type). In contrast, tumors developed after 3 Gy irradiation exhibited interstitial losses around Ptch1 (R-type). A clear dose-dependent increase in the proportion of R-type tumor at intermediate doses suggested R-type to be a reliable radiation signature. Array-CGH analysis indicated the R-type-specific copy-number reduction around Ptch1 and LOH-type-independent frequent gains of whole chromosome 6. Integrated expression microarray analysis indicated that expression levels of many genes within the altered genomic regions faithfully reflected the genomic copy-number changes. Furthermore, it was also suggested that these expression changes in turn influenced on many other genes, such as Tgfb2 and Tgfb3, on widespread genomic regions. This is the first demonstration that radiation-induced tumors developed after low-dose irradiation can be characterized quite precisely by interstitial deletion of Ptch1 and by associated gene expression profile. Three medulloblastomas were analyzed by array-CGH method.
2010-07-14 | E-GEOD-19382 | biostudies-arrayexpress
Project description:Genomic radiation signature illuminates low-dose effects with sharply reflected transcriptome in Ptch1-deficient medulloblastomas. Cancer risks of low-dose radiation are of great concern especially in relation to rapidly increasing medical exposures; however, their accurate assessments cope with many challenges and difficulties, partly due to the inability to distinguish radiation-induced tumors from spontaneous ones. Here, we analyzed the dose-dependent effect of radiation on medulloblastoma development in Ptch1 heterozygous mice on C3B6F1 background. The incidence and latency of medulloblastoma increased and shortened with increasing radiation dose, respectively. Amazingly, radiation contributed to tumorigenesis even at 50 mGy and 100% of mice got medulloblastoma with 1.5 Gy. Loss of heterozygosity (LOH) analysis on a total of 164 tumors indicated that spontaneous tumors showed LOH in broad regions on chromosome 13, including Ptch1 and distally-extending telomeric portion (S-type). In contrast, tumors developed after 3 Gy irradiation exhibited interstitial losses around Ptch1 (R-type). A clear dose-dependent increase in the proportion of R-type tumor at intermediate doses suggested R-type to be a reliable radiation signature. Array-CGH analysis indicated the R-type-specific copy-number reduction around Ptch1 and LOH-type-independent frequent gains of whole chromosome 6. Integrated expression microarray analysis indicated that expression levels of many genes within the altered genomic regions faithfully reflected the genomic copy-number changes. Furthermore, it was also suggested that these expression changes in turn influenced on many other genes, such as Tgfb2 and Tgfb3, on widespread genomic regions. This is the first demonstration that radiation-induced tumors developed after low-dose irradiation can be characterized quite precisely by interstitial deletion of Ptch1 and by associated gene expression profile. Twelve medulloblastomas were analyzed by array-CGH method.
2010-07-14 | E-GEOD-19381 | biostudies-arrayexpress
Project description:DNA methylation might have a significant role in preventing normal differentiation in pediatric cancers. We used a genomewide method for detecting regions of CpG methylation on the basis of the increased melting temperature of methylated DNA, termed denaturation analysis of methylation differences (DAMD). Using the DAMD assay, we find common regions of cancer-specific methylation changes in primary medulloblastomas in critical developmental regulatory pathways, including Sonic hedgehog (Shh), Wingless (Wnt), retinoic acid receptor (RAR), and bone morphogenetic protein (BMP). One of the commonly methylated loci is the PTCH1-1C promoter, a negative regulator of the Shh pathway that is methylated in both primary patient samples and human medulloblastoma cell lines. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) increases the expression of PTCH1 and other methylated loci. Whereas genetic mutations in PTCH1 have previously been shown to lead to medulloblastoma, our study indicates that epigenetic silencing of PTCH1, and other critical developmental loci, by DNA methylation is a fundamental process of pediatric medulloblastoma formation. This finding warrants strong consideration for DNA demethylating agents in future clinical trials for children with this disease.
2009-12-05 | GSE17224 | GEO