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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 28, 2019 |
| Title |
Large 1p36 deletions affecting Arid1a locus facilitate Mycn-driven oncogenesis in a new neuroblastoma model |
| Organism |
Mus musculus |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
Loss of heterozygosity (LOH) at 1p36 is a frequent chromosomal event in a broad range of human cancers with increased incidence observed in nervous system malignancies, including neuroblastoma (NBL). MYCN amplification and 1p36 deletions are highly correlated markers of tumor aggressiveness in NBL. While short distal 1p36 losses are associated with single copy MYCN tumors, larger hemizygous 1p deletions correlate with MYCN amplification, suggesting that two tumor suppressor regions exist in 1p36, a distal and proximal region, which have MYCN-independent and dependent roles. To interrogate this, we genome-edited a proximal candidate, Arid1a, a distal candidate, Chd5, and engineered a syntenic 1p36 LOH deletion in primary mouse NCCs, the likely cell of origin for NBL. Chd5 deletions were found to confer most of the pro-tumorigenic functions of 1p36 LOH in cells expressing endogenous Mycn levels. In contrast, reduced tumor latency in Mycn-driven oncogenesis significantly correlated with the loss of Arid1a. Gene expression analysis found that tumors presenting early onset display a Polycomb Repressive Complex 2 (PRC2) signature and an impaired Trp53 signaling pathway signature. Our findings delineate the tumor suppressor functions of 1p36 LOH in NBL and potentially provide critical insights for the constellation of cancers with 1p36 deletion.
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| Overall design |
Profiling the copy number changes in parental cell lines and tumor samples of neuroblastoma model
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| Contributor(s) |
García-López J, Wallace K, Otero JH, Olsen RR, Wang YD, Finkelstein D, Rehg JE, Davidoff AM, Freeman KW |
| Citation(s) |
31940489 |
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| Submission date |
Nov 29, 2018 |
| Last update date |
Jan 28, 2020 |
| Contact name |
Yong-Dong Wang |
| E-mail(s) |
michael.wang@stjude.org
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| Phone |
9015954224
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| Organization name |
St. Jude Children's Research Hospital
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| Street address |
262 Danny Thomas Pl, MS1135
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38134 |
| Country |
USA |
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| Platforms (1) |
| GPL10449 |
Agilent-027411 SurePrint G3 Mouse CGH Microarray 4x180K (Feature Number version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA507631 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123142_RAW.tar |
145.5 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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