Jean C. Zenklusen, Carolyn Hutter and the Cancer Genome Atlas Team

Researchers at top medical institutions across the nation and around the world have been making seminal breakthroughs in the diagnosis and treatment of some of the deadliest types of cancer, resulting in the development of new therapies and improved patient outcomes.

These discoveries are due in large part to The Cancer Genome Atlas, a groundbreaking joint project of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) that involves a dedicated team of federal employees and contractors, and more than 150 researchers working together at dozens of institutions nationally and internationally.

Now led by Jean Claude Zenklusen of NCI and Carolyn Hutter of NHGRI, this nine-year initiative is the first comprehensive effort to create a detailed catalogue of the genomic changes associated with 33 types of tumors, including breast, stomach, lung, bladder, skin, colon, liver, kidney, cervical and prostate cancer. This is providing scientists with critical information not previously available and has led to important discoveries and life-saving treatments.

“The Cancer Genome Atlas has changed the way we classify and treat tumors and how we develop medicines in the future,” said Dr. Harold Varmus, the former NCI director.

Varmus praised Zenklusen for his deft management skills in handling this complex, landmark project, while Dr. Teri Manolio, director of NHGRI’s Division of Genomic Medicine, said Hutter has played a critical role overseeing all aspects of the DNA sequencing and ensuring “everybody is on board with a collaborative approach.”

Since 2013 when Zenklusen became the director of The Cancer Genome Atlas and Hutter joined as NHGRI’s team leader for the project, the mammoth initiative has surpassed its original goal, completing the collection of nearly 11,500 specimens and mapping the genetic mutations of 33 different cancers.

Based on this genetic information, researchers, physicians and scientists have published 18 tumor-specific marker papers and are now working on the remaining 15. These papers provide an analysis of the data and new discoveries and clinical insights, and are meant to be starting points for the broader research community. Scientists are comparing the DNA of normal tissue and cancer tissue taken from the same patient to gain a better understanding of what makes one cancer different from another.

In 2012, for example, researchers found that one type of breast cancer showed greater genomic similarity to a subtype of ovarian cancer than to other types of breast cancer. This finding demonstrated the potential of analyzing and treating tumors based on their genome characterization, rather than the organ of origin. In another case, doctors already are using DNA sequencing to make decisions on drug therapies to treat lung cancer patients with a tumor-specific mutation.

Stephen Chanock, director of the Cancer Epidemiology and Genetics Division at NCI, said one of Zenklusen’s toughest management challenges has been keeping the multimillion dollar effort on track to be completed by 2016. “The beauty of Jean Claude is that he has kept everyone in the game in the fourth quarter to get this project completed,” said Chanock.

Manolio said Hutter has been instrumental in setting priorities and overcoming a variety of management challenges.

“She has made sure that all of the sequencing and data analysis gets done on time and within budget,” said Manolio. “It has been a tour de force getting everyone on the same page and following the same program to get it all done. She sees solutions that other people don’t see and is able to propose them in a way that people recognize them as necessary.”

Chanock said the atlas has given researchers “the first Google map of cancer,” allowing them to understand the similarities and the complexities among cancers, and the breadth of genetic mutations that drive cancer. By connecting specific genomic changes with specific outcomes, he and others said researchers hope to be able to develop more effective, individualized ways of treating each cancer patient.

“There’s not a person working on cancer research at the basic genetic level who’s not using The Cancer Genome Atlas every day. A lot of the best work being done in cancer genomics is taking the data produced by The Cancer Genome Atlas and understanding it better,” Varmus said.

John Weinstein, chair of the Department of Bioinformatics at MD Anderson Cancer Center in Texas said, “The Cancer Genome Atlas has enriched our senses of all cancers. It is a work of a generation to mine all of this information, and although the project is concluding, it is really just beginning.”

Zenklusen, who lost a cousin to cancer, said having seen cancer firsthand made the disease a personal enemy. “If I can actually forward the field so that less people die and suffer from cancer, that’s my bonus,” he said. “When I hear that somebody, somewhere got a better therapy because of what we found, that’s what I live for.”

Hutter, whose father is a retired pediatric oncologist, said she has always been surrounded by science. “I realized that my love of science is also complemented by a love of figuring out how to help people work together in ways that move fields forward,” Hutter said. “The position I have now gives me such great opportunities to do that.”