Genetic screening

High-throughput retroviral tagging to identify components of specific signalling pathways in cancer.Mikkers, H. et al. Nature Genet. 32, 153?159 (2002)

This paper, together with two more letters in the September issue of Nature Genetics, describes the first in vivo mammalian genetic screens used to identify genes underlying human cancer. Mikkers et al. show the power of using retroviral insertional mutagenesis, together with the complete mouse genome sequence, by identifying genes that can substitute for Pim1 and Pim2 in lymphomagenesis. This strategy is the mammalian equivalent of the powerful yeast, D. melanogaster and C. elegans genetic screens.

Oncogenes

RAF/RAS oncogenes and mismatch-repair status.Rajagopalan, H. et al. Nature 418, 934 (2002)

Activating mutations in a member of the RAF family, BRAF, have been found in a high proportion of melanomas and in other cancers. Rajagopalan et al. report that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in KRAS, and that mutations in BRAF are linked to the ability of these tumours to repair mismatch bases in DNA. These results indicate that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis.

Epidemiology

On the use of familial aggregation in population-based case probands for calculating penetrance.Begg, C. B. J. Natl Cancer Inst. 94, 1221?1226 (2002)

High-risk families with multiple cases of breast cancer or case probands are often used in population-based penetrance studies of BRCA1 and BRCA2 mutations. Begg reviews eight published studies and shows that penetrance estimates from case proband studies are biased towards increased risk. This paper highlights the need to improve the methods that are used to predict cancer risk.

Oncogenes

Distinct requirements for Ras oncogenesis in human versus mouse cells.Hamad, N. M. et al. Genes Dev. 16, 2045?2057 (2002)

Oncogenic Ras stimulates three main classes of effector proteins ? Rafs, PI3-kinase and RalGEFs ? with Rafs generally being the most potent at transforming mouse cells. However, using oncogenic Ras mutants, Hamad et al. found that RalGEF is sufficient for Ras transformation in human cells. The findings indicate that signal-transduction biochemistry studies in mice might have to be revisited to assess applicability to humans, and that RalGEF could be a promising target for anti cancer therapies.