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| Status |
Public on Jul 14, 2010 |
| Title |
Integrated array-CGH and expression microarray analyses on medulloblastomas in heterozygous Ptch1 mice, expression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Gene expression in 3 normal cerebellum tissues and 12 medulloblastomas was measured.
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| Contributor(s) |
Ishida Y, Takabatake T, Kakinuma S, Doi K, Yamauchi K, Kaminishi M, Kito S, Ohta Y, Amasaki T, Moritake H, Kokubo T, Nishimura M, Nishikawa T, Hino O, Shimada Y |
| Citation(s) |
20616149 |
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| Submission date |
Dec 07, 2009 |
| Last update date |
Jan 12, 2017 |
| Contact name |
Takashi Takabatake |
| E-mail(s) |
batake@nirs.go.jp
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| Organization name |
National Institute of Radiological Sciences
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| Street address |
Anagawa 4-9-1, Inage-ku
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| City |
Chiba |
| State/province |
Chiba |
| ZIP/Postal code |
263-8555 |
| Country |
Japan |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE19384 |
Integrated array-CGH and expression microarray analyses on medulloblastomas in heterozygous Ptch1 mice |
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| Relations |
| BioProject |
PRJNA123895 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19360_RAW.tar |
28.9 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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