Antisense therapy

Effects of MYCN antisense oligonucleotide administration on tumorigenesis in a murine model of neuroblastoma. Burkhart, C. A. et al. J. Natl Cancer Inst. 95, 1394–1403 (2003)

One of the main prognostic indicators for neuroblastoma is amplification of the MYCN oncogene. Burkhart et al. found that inhibition of MYCN with antisense oligonucleotides in a human neuroblastoma cell line with amplified MYCN decreased expression of the oncogene and decreased tumorigenesis in a mouse model. Investigation of use of MYCN antisense in children with neuroblastoma is warranted.

Genomic instability

The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Overholtzer, M. et al. Proc. Natl Acad. Sci. USA 100, 11547–11552 (2003)

One of the pathways that the p53 tumour suppressor regulates is the checkpoint response to DNA damage, so loss of p53 can result in genomic instability. Overholtzer et al. show that TP53 mutations do correlate with high levels of genomic instability in human osteosarcomas. Interestingly, however, amplification of MDM2 — an upstream inhibitor of p53 — does not increase genomic instability, indicating that inactivation of p53 by different mechanisms has different effects on genome stability.

Inflammation

Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Balbin, M. et al. Nature Genet. 28 Sept 2003 (doi: 10.1038/ng1249)

Matrix metalloproteinases (MMPs) have an important role in tumour progression. Balbin et al. used mice null for Mmp8 (collagenase-2) — an MMP that is produced by neutrophils during an inflammatory response — to show that Mmp8 protects against development of skin tumours in male mice and female mice with depleted oestrogen. So, inhibitors of MMPs might inhibit not only the tumour promotion effects of the enzymes but also the protective effects, which might explain the lack of success of these agents in clinical trials.

Viruses

Characteristics of Hodgkin's lymphoma after infectious mononucleosis. Hjalgrim, H. et al. N. Engl. J. Med. 349, 1324–1332 (2003)

Epstein–Barr virus (EBV) infection in adolescents can cause infectious mononucleosis, which is associated with an increased risk of developing Hodgkin's lymphoma. Hjalgrim et al. followed patients with infectious mononucleosis for incidence of Hodgkin's lymphoma. EBV-positive patients had an increased risk of developing EBV-positive tumours, but not EBV-negative tumours. The authors conclude that the association between infectious-mononucleosis-related EBV infection and EBV-positive Hodgkin's lymphoma is causal.