Stem cells

Skin carcinoma arising from donor cells in a kidney transplant recipient. Aractingi, S. et al. Cancer Res. 65, 1755–1760 (2005)

Cutaneous tumours arising in female patients who had received a male kidney were examined by quantitative polymerase chain reaction and fluorescence in situ hybridization. Male cells were detected in many cases. A particular carcinoma showed a pattern of male cells that seemed to have arisen from the clonal expansion of a single donor cell. So, stem cells from a grafted organ might migrate to the skin, differentiate into, or fuse with, keratinocytes and then, rarely, undergo neoplastic transformation.

Circadian rhythms

Circadian sensitivity to the chemotherapeutic agent cyclophosphamide depends on the functional status of the CLOCK/BMAL1 transactivation complex. Gorbacheva, V. Y. et al. Proc. Natl Acad. Sci. USA 102, 3407–3412 (2005)

How does the time of day regulate the body's sensitivity to chemotherapeutic agents? Gorbacheva et al. showed that mice lacking functional copies of two main circadian-rhythm-regulating genes, CLOCK and BMAL1, are highly sensitive to treatment with cyclophosphamide at any time of day, unlike controls. This is due to a decrease in the recovery and survival rate of B cells after treatment.

Leukaemia

A sumoylation site in PML/RARA is essential for leukemic transformation. Zhu, J. et al. Cancer Cell 7, 143–153 (2005)

The PML–RARA oncogene causes acute promyelocytic leukaemia (APL) by repressing myeloid differentiation. Zhu et al. find that sumoylation of PML is required for transformation ex vivo. Expression in mice of a PML–RARα mutant that cannot be sumoylated leads to myeloid hyperplasia, but not to leukaemia. The authors show that sumoylation allows recruitment of the potent transcriptional repressor DAXX, indicating a mechanism by which PML–RAR might initiate APL.

Tumorigenesis

The RET/PTC–RAS–BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. Melillo, R. M. et al. J. Clin. Invest. 10 Mar 2005 (10.1172/JCI200522758)

Activating mutations of the oncogenes BRAF or RAS, or fusions of the RET tyrosine receptor kinase are all found in papillary thyroid carcinomas, but never together. Melillo et al. reveal that this is because they function in a linear oncogenic signalling pathway, where RET fusions stimulate RAS-dependent activation of BRAF. This cascade initiates a transcriptional programme in thyroid cells that eventually stimulates proliferation and invasion.