Human cancer cells typically exhibit numerous genetic aberrations, ranging from point mutations through to complete chromosome duplications. Whilst standard genome-wide association studies provide important insights into an individual’s genetic predisposition to cancer, they focus on inherited genetic variation; they do not address the new or ‘acquired’ genetic changes that contribute to cancer developing in specific cells at a specific time. However, since cancerous cells are genetically distinct from other, healthy cells in the same person, these genetic triggers can be assessed by comparing the cancer genome from a patient individual with the inherited genome of that individual.
 
This is exactly what researchers from the Genome Centre at Washington University have just achieved, using cells donated by a women in her 50’s who died of acute myeloid leukaemia [Ley TJ  et al. Nature (2008) 456: 66-71]. The tumour cells were compared with healthy skin cells from the patient, using a high throughput parallel sequencing approach to identify single nucleotide variants (SNVs – including SNPs and indels). Furthermore, both of these genomes were compared with other reference genomes (including the dbSNP database, and the genomes of Venter and Watson) to refine the process and provide a measure of the uniqueness – and therefore importance – of the SNVs.
 
After extensive analysis to weed out false positive results, ten non-silent acquired mutations were identified that were present within genes of the cancer genome but not the healthy skin tissue, of which only two were previously known. The majority of these mutations were present in virtually all of the tumour cells. Three of the newly-discovered mutations were in genes that normally suppress tumour growth, and four were in genes linked to the spread of cancer, strongly supporting a causal link to development of the disease.
 
Comment: Published in the top science journal Nature, this landmark study achieves two firsts: it is not only the first time that a cancer genome has been sequenced, but also the first time that a woman’s complete genome has been published. The technique will be applicable to many other cancers, and opens the door to more targeted genome-wide association studies that may be able to uncover specific genetic triggers for the development of cancer. Although still a long away off, this information could serve as the foundation for improved cancer diagnostics, prognostics and therapeutics.