Vaccines

T cell-mediated suppression of angiogenesis results in tumor protective immunity. Zhou, H. et al. Blood 106, 2026–2032 (2005)

Tumour growth can be inhibited by anti-angiogenic intervention. The authors had previously shown that vaccination with a complete copy of the murine growth factor receptor gene Flk1 triggered the production of antibodies against proliferating endothelial cells in the tumour vasculature. Now they show that the use of an engineered minigene containing only one cytotoxic epitope of Flk1, delivered to mice in a Salmonella-based vector, results in an antibody that prevents angiogenesis and protects against various tumours, but does not cross react with healthy tissue.

Cancer genetics

Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms. Fütterer, A. et al. J. Clin. Invest. 115, 2351–2362 (2005)

Myelodysplastic/myeloproliferative diseases (MDS/MPDs) are a heterogeneous group of myeloid neoplasms that are associated with deletions on chromosome 20q. The authors map the death inducer-obliterator (DIDO) gene to this location and show that all patients with MDS/MPDs have DIDO-expression abnormalities. Furthermore, targeting DIDO in mice caused a disease with symptoms similar to those of MDS/MPDs. These results indicate that DIDO might be a tumour suppressor gene for MDS/MPDs.

Tumorigenesis

Genetic ablation of cyclin D1 abrogates genesis of rhabdoid tumors resulting from Ini1 loss Tsikitis, M. et al. Proc. Natl Acad. Sci. USA 102, 12129–12134 (2005)

Rhabdoid tumours are aggressive paediatric malignancies that arise because of the loss of the tumour suppressor gene INI1. INI1 represses cyclin D1 (CCND1) gene expression, and the authors found that Ini1+/−mice develop rhabdoid tumours that have defective INI1 expression but express CCND1. CCND1 de-repression is therefore important for rhabdoid tumorigenesis.

Telomeres

XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer. Muñoz, P. et al. Nature Genet. 4 September 2005 (10.1038/ng1633)

TRF2, a protein that functions to protect telomeric ends of DNA, paradoxically induces increased rates of skin cancer when overexpressed in mouse skin. The authors show that TRF2 interacts with the ultraviolet light-induced DNA repair nuclease XPF and activates XPF function at telomeres. This leads to disruption of the telomere structure and shortening of the telomeres. In addition, TRF2 is also overexpressed in human tumours, indicating that it can be oncogenic in man.