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Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer
- J. Jonkers, R. Meuwissen, H. Gulden, H. Peterse, M. Valk, A. Berns
- BiologyNature Genetics
- 1 December 2001
The results show that inactivation of BRCA2 and of p53 combine to mediate mammary tumorigenesis, and indicate that disruption of the p53 pathway is pivotal in BRCa2-associated breast cancer.
Landscape of somatic mutations in 560 breast cancer whole genome sequences
This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operative, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers
This work identifies p53-binding protein 1 (53BP1) as an essential factor for sustaining the growth arrest induced by Brca1 deletion, and finds reduced 53BP1 expression in subsets of sporadic triple-negative and BRCA-associated breast cancers, indicating the potential clinical implications of these findings.
Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum.
- S. Marino, M. Vooijs, H. van der Gulden, J. Jonkers, A. Berns
- Biology, MedicineGenes & Development
- 15 April 2000
It is demonstrated that loss of function of RB is essential for medulloblastoma development in the mouse and strongly support the hypothesis that medullOBlastomas arise from multipotent precursor cells located in the EGL.
Patient-derived xenograft models: an emerging platform for translational cancer research.
The current state of the art in this field is summarized, including methodologic issues, available collections, practical applications, challenges and shortcomings, and future directions, and a European consortium of PDX models is introduced.
Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1-mutated basal-like breast cancer
- Xiaoling Liu, H. Holstege, J. Jonkers
- BiologyProceedings of the National Academy of Sciences
- 17 July 2007
Conditional mouse models with tissue-specific mutation of Brca1 and/or p53 in basal epithelial cells resulted in the rapid and efficient formation of highly proliferative, poorly differentiated, estrogen receptor-negative mammary carcinomas with pushing borders and increased expression of basal epitocyte markers, reminiscent of human basal-like breast cancer.
REV7 counteracts DNA double-strand break resection and affects PARP inhibition
This work shows that loss of REV7 in mouse and human cell lines re-establishes CTIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, which is reversed by ATM kinase inhibition.
Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells
It is shown that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2- deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells, but PTIP deficiency does not restore homologous recombination activity at double-strand breaks.
High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs
- S. Rottenberg, J. Jaspers, J. Jonkers
- Biology, MedicineProceedings of the National Academy of Sciences
- 4 November 2008
In vivo efficacy of AZD2281 against BRCA1-deficient breast cancer is demonstrated and how GEMMs of cancer can be used for preclinical evaluation of novel therapeutics and for testing ways to overcome or circumvent therapy resistance is illustrated.
Axin and Frat1 interact with Dvl and GSK, bridging Dvl to GSK in Wnt‐mediated regulation of LEF‐1
The observation that the Dvl‐binding domain of either Frat1 or Axin was able to inhibit Wnt‐1‐induced LEF‐1 activation suggests that the interactions between Dvl and Axin and between DVL and Frat may be important for this signaling pathway.