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Genome Code Cracked for Breast and Colon Cancers

er than normal variations or minor changes with no effect on the gene product.

In total, the Hopkins team combed through 465 million nucleotides – several encyclopedias’ worth of letters – to find approximately 1,500 DNA nucleotides that differed from the normal code in important ways. Virtually all these mistakes were mere single-nucleotide 'typos.' Some 200 genes were significantly mutated; the mutated genes in breast and colon cancers were almost completely distinct, suggesting very different pathways for the development of each of these cancer types.

Says Kinzler, 'This gives us some understanding of why breast and colon cancers, and most likely other cancers as well, are very different diseases and develop through different processes. When we say this will drive cancer research for the next couple of decades, this is one of the reasons. Now researchers will study how these mutations occur in breast and colon cancers, perhaps searching for environmental agents or cellular processes that drive these changes.'

The Hopkins team also found that the average number of mutant genes in each cancer is about 100, and at least 20 are likely to be crucial for tumor formation. 'Each cancer has a different blueprint,' says Velculescu. 'No two patients are identical.'

Other cancers also can be evaluated using the Hopkins approach, which they say has been developed over the past two decades and made possible through recent advances in DNA sequencing and bioinformatics.

'These findings will guide and provide support for future comprehensive genetic studies including those envisioned by The Cancer Genome Atlas Project,' says Vogelstein. Future research will include performing similar analyses on other tumors types, charting the pathways through which each mutant gene acts, and looking for common mutations that can be targeted with cancer drugs or used to detect the disease earlier.



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