Cancer genomics

Throughout life, the cells in every individual accumulate many changes in the DNA inherited from his or her parents. Certain combinations of changes lead to cancer. During the last decade, the cost of DNA sequencing has been dropping by a factor of 10 every two years, making it now possible to read most of the three billion base genome from a patient's cancer tumor, and to try to determine all of the thousands of DNA changes in it. Under the auspices of NCI's Cancer Genome Atlas Project, 10,000 tumors will be sequenced in this manner in the next few years. Soon cancer genome sequencing will be a widespread clinical practice, and millions of tumors will be sequenced. A massive computational problem looms in interpreting these data.

First, because we can only read short pieces of DNA, we have the enormous problem of assembling a coherent and reliable representation of the tumor genome from massive amounts of incomplete and error-prone evidence. This is the first challenge. Second, every human genome is unique from birth, and every tumor a unique variant. There is no single route to cancer. We must learn to read the varied signatures of cancer within the tumor genome and associate these with optimal treatments. Already there are hundreds of molecularly targeted treatments for cancer available, each known to be more or less effective depending on specific genetic variants. However, targeting a single gene with one treatment rarely works. The second challenge is to tackle the combinatorics of personalized, targeted, combination therapy in cancer.