Epigenetics

Transcriptional silencing of Polo-like kinase 2 ( SNK/PLK2 ) is a frequent event in B-cell malignancies. Syed, N. et al. Blood 107, 250–256 (2006)

The Polo-like kinases (PLKs) regulate cell-cycle and DNA-damage-induced checkpoints, but their function as tumour suppressors in human cancers has not been confirmed. This paper demonstrates that PLK2 is transcriptionally downregulated in B-cell malignancies owing to the aberrant methylation of a CpG island located in the 5′ end of PLK2. Restoration of PLK2 expression in these cells induced apoptosis, indicating why expression of this gene is selected against.

Signalling

A role for the scaffolding adapter GAB2 in breast cancer. Bentires-Alj, M. et al. Nature Med. 12, 114–121 (2006)

The transduction of many extracellular signals is enhanced by scaffolding adaptors. The gene that encodes one adaptor, GRB2-associated binding protein 2 (GAB2), maps to 11q13–14, a region that is commonly amplified in breast cancer. The authors show that overexpression of GAB2 induces proliferation of non-transformed mammary cell lines and increases tumour growth in ERBB2 mouse models of breast cancer. Therefore, GAB2 overexpression might be an important consequence of 11q13 amplification in human breast cancers.

Stem cells

Decatenation checkpoint deficiency in stem and progenitor cells. Damelin, M., Sun, Y. E., Sodja, V. B. and Bestor, T. H. Cancer Cell 8, 479–484 (2005)

The decatenation checkpoint delays entry into mitosis until chromosomes have been disentangled. Tim Bestor and colleagues have evidence that the efficiency of this checkpoint is reduced in undifferentiated cells such as stem cells. They show that embryonic stem cells often complete cell division with entangled chromosomes, resulting in aneuploid daughter cells. This deficiency probably increases the rate of chromosome aberrations in cancer stem cells.

Biomarkers

Pre-operative serum tissue factor levels are an independent prognostic factor in patients with ovarian carcinoma. Han, L. Y. et al. J. Clin. Oncol. 27 Dec 2005 (10.1200/JCO.2005.02.9181)

Tissue factor, a blood coagulant, is implicated in regulating tumour angiogenesis. Han et al. examined whether preoperative levels of tissue factor could serve as a prognostic marker in ovarian cancer patients. They assayed tissue-factor serum levels in 98 women with invasive epithelial carcinoma, 30 with low-malignant-potential tumours and 16 with benign tumours. A validation group of 39 women with metastatic ovarian cancer was also analysed. The results show that tissue-factor serum levels ≥190 pg ml−1 are significantly associated with decreased patient survival and that an increased pre-operative tissue-factor serum level is an independent prognostic factor for death from disease.