Chromosome instability

Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosome instability. Shin, H.-J. et al. Cancer Cell 4, 483–497 (2003)

The mitotic checkpoint prevents chromosome instability by delaying anaphase until all chromosomes are properly attached to the mitotic spindle. Shin et al. show that BubR1, a component of the mitotic checkpoint machinery, is significantly reduced in cancer cells causing polyploidy. Its expression triggered apoptosis in polyploid cells and inhibited growth of polyploid tumours in mice, indicating that loss of BubR1 contributes to tumorigenesis.

Metastasis

The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. Tian, E. et al. N. Engl. J. Med. 349, 2483–2494 (2003)

Multiple myeloma (MM) cells metastasize to bone and produce osteolytic lesions, by shifting the normal balance between osteoblasts, which control bone formation, and osteoclasts, which control bone resorption. Tian et al. identified four genes that were overexpressed in plasma cells from patients with osteoclastic lesions, including Dikkopf1 (DKK1) — a secreted factor that inhibits skeletal development. DKK1 was detected in MM cells and inhibited the differentiation of osteoblastic precursors in vitro. So, by blocking osteoblast differentiation, DKK1-expressing MM cells promote osteoclast proliferation and osteolysis.

Gene expression

Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. Iacobuzio-Donahue, C. A. et al. Cancer Res. 63, 8614–8622 (2003)

Iacobuzio-Donahue et al. combined data obtained from oligonucleotide gene arrays, complementary DNA arrays and serial analysis of gene expression to identify genes that are highly expressed in pancreatic cancer. This approach identified robust changes in gene expression and produced a set of six genes that might prove to be clinically useful for pancreatic cancer.

Gene therapy

Gene therapy insertional mutagenesis insights. Davé, U. P., Jenkins, N. A. & Copeland, N. G. Science 303, 333 (2004)

Three years after retroviral gene therapy cured nine children with X-linked severe immunodeficiency, two of the children developed T-cell leukaemia, which was caused by integration of the retrovirus near the known T-cell oncogene LMO2, which increases its expression. Davé and colleagues now show that the interleukin-2 receptor G gene, which is contained in the retrovirus, also has a role in the development of leukaemia, providing a genetic explanation for the high frequency of leukaemia that is observed in the gene-therapy trials.