Methylation

Reduced rates of gene loss, gene silencing and gene mutation in Dnmt1-deficient embryonic stem cells. Chan, M. F. et al. Mol. Cell. Biol. 21, 7587–7600 (2001) [PubMed]

DNA methylation is an important way of inactivating tumour-suppressor genes, but what effect does it have on mutation rates? Using a model system in which loss of function for a transgene is selected for in the presence and absence of DNA methyltransferase 1 (Dnmt1), Chan and colleagues show that rates of both gene loss and missense mutation are reduced in Dnmt1-deficient cells, which might explain why reduced methyltransferase levels prevent polyposis in some mouse models of colorectal cancer.

Epidemiology

Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease Collaborative group on Hormonal Factors in Breast Cancer. Lancet 388, 1389–1399 (2001) [PubMed]

This meta-analysis provides encouraging news for women with a family history of breast cancer: although the risk of developing breast cancer increases with the number of affected first-degree relatives, eight out of nine women who develop breast cancer don't have an affected relative, and most women with an affected relative will never develop the disease.

Diagnostics

BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia Tanner S. M. et al. Proc. Natl Acad. Sci. USA 98, 13901–13906 (2001) [PubMed]

Tanner et al. have used representational difference analysis of mRNA from acute myelogenous leukaemia patients, to find a highly conserved mammalian gene, BAALC, that is overexpressed in human leukaemic blast cells. In normal tissue, the gene is expressed in neuroectoderm-derived tissues, and the protein localizes to the cytoskeletal network. Although little is known about BAALC function, high levels of expression were associated with poor prognosis in leukaemia patients.

Radiation resistance

Genes required for ionizing radiation resistance in yeast. Bennett, C. B. et al. Nature Genet. 29, 426–434 (2001) (DOI:10.1038/ng778) [Contents page]

Resistance to radiotherapy has long been a major drawback for its treatment of cancer. But now, a new study in yeast has identified genes that could be involved in this resistance. Bennett et al. screened yeast that were homozygously deleted for nonessential genes, after exposure to γ-irradiation. They identified 107 new genes, many of which affect replication, recombination and checkpoint functions. Of these, 69 show some homology to human genes, and 17 have been implicated in cancer. Further analysis of these genes could provide insight into the mechanisms of radiation resistance.