Genomic instability and the selection of treatments for cancer

A critical link exists between DNA mutation and chromosomal rearrangements (genomic instability) and cancer development. This genomic instability can manifest itself as small changes at the nucleotide level or as gross chromosomal alterations. Mutations in the genes that encode DNA damage response proteins are responsible for a variety of genomic instability syndromes including hereditary non-polyposis colorectal carcinoma, Bloom's syndrome, ataxia-telangiectasia, BRCA-associated breast and ovarian cancers and Fanconi anaemia. Similarly, epigenetic silencing of genes associated with the maintenance of genomic stability have also been implicated in the pathogenesis of cancer. Here, we discuss how different tumours may be classified not only by tumour site but also by the type of underlying genetic instability. This type of classification may assist in the optimization of existing treatment regimens as well as informing the development of new therapeutic approaches. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.