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| Status |
Public on Nov 28, 2018 |
| Title |
Mammary Tissue: aCGH of primary (IGF-IR induced) and recurrent (IGF-IR independent) mammary tumors from MTB-IGFIR mice |
| Organism |
Mus musculus |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
Tumor recurrence represents a significant clinical challenge in the treatment and management of breast cancer. To investigate whether copy number aberrations (CNAs) facilitate the re-emergence of tumor growth from residual disease we performed array comparative genomic hybridization (aCGH) on primary and recurrent mammary tumors from an inducible mouse model of type-I insulin-like growth factor receptor (IGF-IR) driven breast cancer. This genome-wide analysis revealed primary and recurrent tumors harbored distinct copy number aberrations (CNAs) with relapsed tumors containing an increased number of gene-level gains and losses. Remarkably, CNAs detected in primary tumors were largely devoid of annotated cancer genes while the vast majority of recurrent tumors harbored at least one CNA containing a known oncogene or tumor suppressor. Specifically, a subset of recurrent tumors carried gains at 6qA2 and 9qA2 which encode the Met and Yap1 oncogenes respectively. The most frequent CNA detected was a focal deletion at 4qC5 involving the Cdkn2a and Cdkn2b tumor suppressor genes. Integrative analysis revealed positive correlations between gene copy number and mRNA expression suggesting Met, Yap1 and Cdkn2a/b may serve as potential driver genes that promote tumor recurrence. Together, these findings indicate that tumor recurrence is facilitated by the acquisition of CNAs with oncogenic potential and provide a framework to dissect the molecular mechanisms that mediate tumor escape from dormancy.
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| Overall design |
Two-color common reference design with 11 primary tumors (doxycycline-dependent) and 8 recurrent tumors (doxycycline-independent) from MTB-IGFIR mice.
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| Contributor(s) |
Jones R, Moorehead R |
| Citation(s) |
30597648 |
| |
| Submission date |
Sep 19, 2018 |
| Last update date |
Feb 27, 2019 |
| Contact name |
Roger Moorehead |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Guelph
|
| Department |
Biomedical Sciences
|
| Street address |
50 Stone Rd E
|
| City |
Guelph |
| ZIP/Postal code |
N1G2W1 |
| Country |
Canada |
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| Platforms (1) |
| GPL15076 |
Agilent-014695 Mouse Genome CGH Microarray 244A (G4415A)(Probe Name version) |
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| Samples (19)
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| Relations |
| BioProject |
PRJNA491906 |
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