Oncogenes

High frequency of mutations of the PIK3CA gene in human cancers. Samuels, Y. et al. Science 11 Mar 2004 (doi:10.1126/science.1096502)

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate signalling pathways involved in proliferation, survival and motility. To determine if they are mutated in cancer cells, Samuels et al. sequenced PI3K genes in hundreds of tumour samples and found that it is mutated in a large percentage of colon, brain, gastric, breast and lung cancers. PI3K is therefore likely to be an oncogene that can be targeted therapeutically or analysed in early detection and prognosis.

Carcinogenesis

The stroma as a crucial target in rat mammary gland carcinogenesis. Maffini, M. V. et al. J. Cell Sci. 117, 1495–1502 (2004)

Carcinogens can cause mutations in epithelial cells and can alter epithelial–stromal cell interactions, but which process is important for tumour formation? Using a rat mammary-tissue-recombination model and N-nitrosomethylurea (NMU), Maffini et al. show that stromal cells exposed to NMU in vitro can transform normal mammary epithelial cells in vivo, whereas NMU-treated epithelial cells form normal ducts in vivo. This work indicates that the stroma is an important target of carcinogens.

Immunotherapy

Immunoprevention of basal cell carcinomas with recombinant hedgehog-interacting protein. Vogt, A. et al. J. Exp. Med. 199, 753–761 (2004)

Abnormal hedgehog signalling causes basal-cell carcinomas (BCCs). The authors found that hedgehog-interacting protein (Hip1) is overexpressed in BCCs in the Ptch+/− mouse model of this disease. Ptch+/− mice immunized with Hip1 polypeptides produce effective B-cell and T-cell immune responses that reduce the number of BCCs. Immunization with proteins that are upregulated by the hedgehog pathway could therefore prevent BCC in people who are genetically predisposed to developing this type of tumour.

Tumorigenesis

Epigenetic differences between Wilms' tumour in white and east-Asian children. Fukuzawa, R. et al. Lancet 363, 446–451 (2004)

Asian children who develop Wilms' tumours are younger than children of other races and are predominantly male. Imprinting of the maternal insulin-like growth-factor gene (IGF2) is lost in some Wilms' tumours, so the authors investigated whether the frequency of this loss of imprinting (LOI) explains these interethnic differences. IGF2 LOI and associated precancerous lesions occur at a low frequency in children of east-Asian origin and a high frequency in Caucasian children, indicating that tumorigenesis is occurring by two distinct mechanisms.