The changing landscape of the cancer genome

It has been a big year in the world of sequencing cancer genomes. And if you attended the recent Keystone Symposium in Boston, “The Changing Landscape of the Cancer Genome, ” it’s only getting bigger – fast. The symposium focused on discoveries coming from large-scale cancer genomic efforts. “A year...

It has been a big year in the world of sequencing cancer genomes. And if you attended the recent Keystone Symposium in Boston, “The Changing Landscape of the Cancer Genome,” it’s only getting bigger – fast. The symposium focused on discoveries coming from large-scale cancer genomic efforts. “A year ago we had the first glimpses of the cancer genomes in studies of just one to five patients,” says Jesse Boehm, assistant director of the Broad’s Cancer Program who attended the symposium along with several other Broadies, many of whom gave presentations. But in the past year, studies analyzing completely sequenced genomes of 10-20 tumors per tumor type started to come out. And within the last few months, studies involving tens to a hundred or more tumor genomes are being reported at meetings, with a few reaching publication. “The findings coming out of these studies are really phenomenal and we’re starting to really achieve the promise of cancer genomics,” Jesse says. “There is unbridled enthusiasm that we’re finally going to have this whole catalog of information and now we have to figure out how to interpret this flood of exciting data to help cancer patients.”

Lynda Chin, senior associate member at the Broad Institute and Scientific Director at the Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute (DFCI), who helped organize the conference couldn’t agree more. Lynda explains, “The take home message is that finally we are seeing the fruits coming out of these large-scale efforts.”

One of the efforts Lynda referred to is the Cancer Genome Atlas (TCGA), the first large-scale cancer genome study, which has published pilot study results in the field of glioblastoma genome analysis. Just last week, TCGA published its first findings in the field of ovarian cancer in a paper in Nature. (Read more about it in the Broad news story here.) “These large studies are clearly transforming the way we do genomic analysis,” she says. “They are yielding invaluable knowledge and highlighting the power of international collaborative efforts, like TCGA.” Lynda adds, “We are finally getting traction on how to do large-scale genome analysis and the data stream is going to explode over the next 12 months. So much so that having a near complete catalog of the human cancer genome is not a dream any longer.”

Two major themes were evident at the meeting. The first is that rapid advances in sequencing technology are now translating into cancer discoveries.“It is very clear that with all the new advances in sequencing we’re able to understand cancer biology like never before,” Jesse says. “Incredible advances in sequencing technology are really translating into cancer discovery.” The Broad’s Stacey Gabriel, head of cancer and medical sequencing, and Wendy Winkler, director of the genetic analysis platform, highlighted just how quickly advances in next-generation sequencing are moving the field ahead, not just in cancer but in all areas of genome sequencing.

But producing reams of data is obviously not the end game. The second major theme involves an ongoing discussion about how best to understand the biological consequences of cancer genome data. Lynda explains that the idea of network modeling is essential to putting all of the data coming from TCGA and other cancer genome studies into an accessible framework. “Knowledge is not the same thing as understanding,” she says. Jesse agrees that a major challenge in data analysis and computational biology is at hand. “Sequencing is not the cost-limiting factor anymore,” Jesse said. He believes that building computational algorithms to interpret the information and then performing laboratory experiments at large scale are the next major challenges in cancer genome analysis.