Mouse Lymphoblastic Leukemias Induced by Aberrant Prdm14 Expression Demonstrate Widespread Copy Number Alterations Also Found in Human ALL
Abstract
:1. Introduction
2. Results and Discussion
Sample # | Tumorlocation | IgHrearrangement | TCRrearrangement | Histological abnormalities | BCR/TCR-based tumor type |
---|---|---|---|---|---|
91 (control) | Spleen | N/A | N/A | None | N/A |
92 (control) | Spleen | N/A | N/A | None | N/A |
93 (control) | Spleen | N/A | N/A | None | N/A |
MPr14-111 | Lymph node | No | No | LL | Common Lymphoid Progenitor (CLP)-like |
MPr14-143 | Spleen | Yes | No | LL with erythroblastosis | Precursor-B |
MPr14-147 | Spleen | Yes | Yes | LL | Mixed |
MPr14-148 | Lymph node | No | Yes | LL with erythroblastosis | Precursor-T |
MPr14-185 | Lymph node | Yes | No | LL | Precursor-B |
MPr14-189 | Lymph node | Yes | No | LL | Precursor-B |
MPr14-196 | Spleen | Unknown | Unknown | LL with erythroblastosis | Unclassified |
MPr14-197 | Spleen | Yes | Yes | LL | Mixed |
MPr14-217 | Lymph node | Yes | No | LL | Precursor-B |
MPr14-218 | Lymph node | Yes | No | LL-pleiomorphic | Precursor-B |
MPr14-228 | Spleen | Yes | Yes | LL with increased megakaryocytes | Mixed |
MPr14-258 | Spleen | No | Yes | LL | Precursor-T |
2.1. PRDM14-Induced Tumors Have Numerous, Recurrent Copy Number Alterations with Occasional Aneuploidy
2.2. Deleted Genes Confirm Role of B-Cell Developmental Disruption in PRDM14-Induced Lymphomagenesis
2.3. Deletions and Amplifications Occur in Characterized Tumor Suppressors and Oncogenes
Tumor # | Cytogenetics | BCR/TCR-based tumor type | Oncogene amplifications | Tumor suppressor deletions | Fragile site gene CNA | MLL rearrangement partners amplified |
---|---|---|---|---|---|---|
MPr14-111 | 40,XX | CLP-like | Ebf1, Cdkn2a | Lpp | ||
MPr14-143 | 40,XX | Precursor-B | Eg5 | |||
MPr14-185 | 43,XY,+14,+15,+17 | Precursor-B | Eg5, Tbx2 | Cdkn2a | Mllt10 | |
MPr14-189 | 40,XY,del(18qD1→qter), del(19qter→qB) | Precursor-B | Tbx2 | Mllt10, Ell, Mllt3 | ||
MPr14-217 | 40,XY | Precursor-B | Notch1, Tcf3, Tbx2 | Ebf1 | Grid2 | |
MPr14-218 | 41,XY,+1 | Precursor-B | Ebf1 | Wwox | Ell | |
MPr14-148 | 40,XX | Precursor-T | Eg5 | |||
MPr14-258 | 40,XX | Precursor-T | Eg5 | Ell, Eps15, Lpp | ||
MPr14-147 | 42,XX,+14,+15 | Mixed | Eg5 | Pax5 | Grid2 | Mllt10 |
MPr14-197 | 40,XY | Mixed | Mycl1, Eg5, Tbx2 | Cdkn2a, Fhit | Fhit | Mllt10, Lpp |
MPr14-228 | 41,XY,+2 | Mixed | Lmo1 | Ikzf1 | Wwox | Mllt10, Ell, Lpp |
MPr14-196 | 40,XY | Unclassified | Lmo1, Eg5 | Cdkn2a |
2.4. T-lineage Lymphoblastic Leukemia/Lymphoma Demonstrate Fewer Candidate Driver Mutations than Precursor B or Mixed Lineage Leukemias
2.5. Gene Amplifications and Deletions Occur at PRDM14 Binding Loci
2.6. Extensive Amplification of Known Cancer Rearrangement Partners
2.7. Genes Involved in Maintaining Chromosomal Stability Have Decreased Expression Prior to Leukemia Formation, and DNA Damage Response Fails to Activate
2.8. Discussion
3. Experimental Section
3.1. Animal Care
3.2. Transduction of Prdm14 into Stem-Cell Enriched Bone Marrow Cells
3.3. Array CGH
3.4. Gene Expression Array
3.5. Gene Expression Studies
4. Conclusions
Acknowledgments
Supplementary Materials
References
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Simko, S.J.; Voicu, H.; Carofino, B.L.; Justice, M.J. Mouse Lymphoblastic Leukemias Induced by Aberrant Prdm14 Expression Demonstrate Widespread Copy Number Alterations Also Found in Human ALL. Cancers 2012, 4, 1050-1066. https://doi.org/10.3390/cancers4041050
Simko SJ, Voicu H, Carofino BL, Justice MJ. Mouse Lymphoblastic Leukemias Induced by Aberrant Prdm14 Expression Demonstrate Widespread Copy Number Alterations Also Found in Human ALL. Cancers. 2012; 4(4):1050-1066. https://doi.org/10.3390/cancers4041050
Chicago/Turabian StyleSimko, Stephen J., Horatiu Voicu, Brandi L. Carofino, and Monica J. Justice. 2012. "Mouse Lymphoblastic Leukemias Induced by Aberrant Prdm14 Expression Demonstrate Widespread Copy Number Alterations Also Found in Human ALL" Cancers 4, no. 4: 1050-1066. https://doi.org/10.3390/cancers4041050