Sequence-based advances in the definition of cancer-associated gene mutations

Recent rapid progress in DNA sequencing has permitted projects to be undertaken that are aimed at building unbiased genome-wide portraits of the underlying mutations in human tumors. This review sets out the highlights of the recent progress in this area and the rapidly evolving picture of the underlying genetic basis of human epithelial cancers.

Individual tumors are estimated to contain around 80 point mutations in protein coding genes of which 15 are likely to be tumorigenic. It is likely that there are hundreds of different genes that when mutated contribute to human tumorigenesis most in only a small fraction of tumors. Mutations caused by large chromosomal rearrangements also appear to be common in tumors. In prostate and lung cancers, recurrent chromosomal translocations resulting in tumorigenic fusion proteins have been identified.

The multitude of new mutated genes being identified in human tumors represent many new directions for experimental research into the molecular pathways that lead to tumor formation. These studies, in turn, are likely to lead to many novel approaches to targeted therapy useful in subsets of tumors with particular types of gene mutation.