Distinguish Between the Effects of Mutation and Selection in Cancer Genomes

An international research team

describes how structural signatures can be used to distinguish between the effects of mutation and selection in cancer genomes. Graham Bignell of the Wellcome Trust Sanger Institute and his colleagues identified 2,428 somatic homozygous deletions in 746 cancer cell lines. They then elicited “structural signatures that distinguish between homozygous deletions over recessive cancer genes and fragile sites.” The team writes that the application of these signatures to unexplained homozygous deletions revealed that many exist in regions of inherent fragility.

Also in Nature this week, a team led by researchers at the Broad Institute report that cancer cells containing amplifications surrounding MCL1 and BCL2L1 ― anti-apoptotic genes ― depend on those genes for survival. They also describe their discovery that many somatic copy-number alterations recognized in individual cancer types are present in several other cancers.

Arjun Raj of the University of Pennsylvania (formerly of MIT) and his colleagues discuss mutations in developmental networks and how they can expose variability in gene expression ― and subsequently phenotypic variation. In their study, Raj’s team examined intestinal specification in Caenorhabditis elegans, the model nematode in which cell fate is controlled by a small transcriptional network. They write that “mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, whereas others produce intestinal precursors.” Raj et al. also describe their elucidation of an apparent on/off expression pattern of the master regulatory gene of intestinal differentiation in C. elegans.

Meanwhile, in Nature Biotechnology, researchers present an approach for associating genes with plant traits using a genome-scale functional network and targeted reverse genetic screening in Arabidopsis thaliana. The network, dubbed AraNet, creates predictive associations among diverse biological pathways in the model plant which outperform those derived from published literature. The paper also identifies AT1G80710 (now known as DRS1) as a drought-sensitivity regulator and AT3G05090 (LRS1) as critical in lateral root development and regulation.

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