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| Status |
Public on May 17, 2023 |
| Title |
DNA sequences at integration sites in primary mammary tumors and lung metastases from a sleeping-beauty transposon-mediated mutagenesis screen on Rb-deficient background |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
This deposition describes DNA sequences at integration sites in primary tumors and lung metastases from a sleeping-beauty transposon-mediated mutagenesis screen on Rb-deficient background in the mammary gland in MMTV-Cre:Rbf/f:T2/Onc3a:R26lsl_SB11 and MMTV-Cre:Rbf/f:T2/Onc3b:R26lsl_SB11 female mice. In these mice, Rb floxed (Rbf/f) alleles and a SB11 transposase, knocked into the ROSA26 locus (R26lsl_SB11), are mobilized via MMTV-Cre. Two different transgenic transposon concatemers, T2/Onc3a and T2/Onc3b, containing 11 and 28 copies on chromosomes 9 and 12 were used so that local hoping in the respective chromosomes can be discarded. These mice developed large primary tumors and macroscopic lung metastases; biopsies from the primary tumors and entire lung metastases were used to extract DNA. The DNA was subjected to sonication, ligation-mediated PCR with 79 bar coded primers, followed by next-generation DNA sequencing. We identified Primary-specific and lung Metastasis-specific gene-centric Common Integration Sites (gCIS) as well as shared gCIS, observed in both primary mammary tumors and lung metastases. Using sequence analysis of integration sites, we were able to demonstrate in multiple cases clonal relationship between primary lesions and metastases. The metastatic gCIS form specific hubs that may be prioritized for targeted therapy. For details, see reference below.
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| Overall design |
Sleeping Beauty (SB) screens in Rb-deficient model of breast cancer
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| Contributor(s) |
Jiang Z, Skowron P, Zhang J, Taylor MD, Zacksenhaus E |
| Citation(s) |
37463901 |
| |
| Submission date |
May 10, 2023 |
| Last update date |
Jul 28, 2023 |
| Contact name |
Eldad Zacksenhaus |
| E-mail(s) |
eldad.zacksenhaus@utoronto.ca
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| Organization name |
University Health Network
|
| Street address |
101 College Street
|
| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 1L7 |
| Country |
Canada |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA971155 |
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