Oncogenesis

The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Ruggero, D. et al. Nature Med. 18 April 2004 (doi:10.1038/nm1042)

The translation factor eIF4E has been implicated in tumorigenesis. Ruggero et al. showed that transgenic expression of eIF4E causes mice to develop B-cell lymphomas, as well as other tumour types. They found that c-Myc cooperates with eIF4E to promote lymphomagenesis, and propose a model in which c-Myc overrides eIF4E-induced cellular senescence and eIF4E antagonizes c-Myc-dependent apoptosis.

Diagnostics

A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression. Cerutti, J. M. et al. J. Clin. Invest. 113, 1234–1242

The techniques that are used at present to biopsy thyroid nodules can not distinguish between benign follicular thyroid adenoma and invasive follicular carcinoma, so patients with follicuar lesions undergo thyroid resection. Cerutti et al. used serial analysis of gene expression to identify genes that were differentially expressed in the two tumour types, and could therefore improve diagnosis. They showed that a combination of genes can be used to identify carcinomas with 83% accuracy, so this approach might spare patients from unnecessary surgery.

Oncogenesis

Germ-line expression of an oncogenic erbB2 allele confers resistance to erbB2 -induced mammary tumorigenesis. Andrechek, E. R. et al. Proc. Natl Acad. Sci. USA 101, 4984–4989 (2004)

Mammary-specific expression of an activated ErbB2 allele leads to the formation of mammary adenocarcinomas. Andrechek et al. tested the effect of expressing the same allele in the germline. Despite levels of ErbB2 expression in the mammary epithelium comparable to those of animals with tissue-specific activation, mice carrying germline ErbB2 did not develop tumours. The authors suggest that feedback mechanisms during development compensate for germline oncogene expression.

Epigenetics

Germline epimutation of MLH1 in individuals with multiple cancers. Suter, C. M. et al. Nature Genet. 4 April 2004 (doi:10.1038/ng1342)

Epigenetic silencing of tumour suppressors can lead to cancer. Suter et al. identified two individuals with histories of colorectal cancer who had soma-wide epigenetic inactivation of the DNA mismatch repair gene MLH1, indicating that germline epimutation can lead to cancer predisposition. Spermatozoa from one of these individuals also carried the MLH1 epimutation, indicating that this type of defect can be transmitted to offspring.