The UNC Lineberger Comprehensive Cancer Center is leading a national, multi-year, collaborative effort to characterize the genetic changes in nearly 30 cancer types. Earlier this year, UNC Lineberger hit a milestone in this effort – sequencing 10,000 samples of cancer tumor tissue.
UNC sequenced the RNA for 10,000 tumor samples as part of The Cancer Genome Atlas project, a National Cancer Institute and National Human Genome Research Institute-backed effort to create a comprehensive atlas of the genetic changes in cancer.
The work helped lay the foundation for groundbreaking research completed as part of TCGA. And with approximately 10,000 of the samples sequenced by UNC uploaded to a public database accessible to researchers around the world, the work is expected to continue to fuel new discoveries.
“We expect that the data that UNC gathered for this large-scale sequencing project will be an active discovery resource that scientists use to discover new things for at least another decade, and potentially for more,” said D. Neil Hayes, MD, MPH, a UNC Lineberger member and an associate professor of clinical research in hematology and oncology at the UNC School of Medicine.
UNC was able to hit the milestone because of key investments in next-generation sequencing technology, Hayes said, as well as because it had the staff to operate that technology and the leadership of key scientific investigators.
“No. 1, it was scientific leadership that made this project possible, and No. 2, it was production capacity,” Hayes said. “We had to have the resources to be able to handle roughly 200 samples a month on the sequencing side and on the analytics side, as well as storage space, sequencers, computers, project management expertise – and many of these things were supported by cancer center resources and the state of North Carolina.”
Investments in next-generation sequencing technology from the state-funded University Cancer Research Fund were “crucial,” said Piotr Mieczkowski, director of UNC’s High Throughput Sequencing Facility and a research assistant professor of genetics. The University Cancer Research Fund helped UNC to buy faster, more efficient sequencers.
“You have to remember that when everything was happening, next-generation sequencing technology was really very, very new,” Mieczkowski said. “In just a few years, we have built real knowledge of how to create various types of libraries and how to perform sequencing on a large scale.”
Specifically, the major piece of the work that UNC did to support the project was to sequence RNA, which is the genetic code that carries instructions from DNA for making proteins. Sequencing of RNA allows for researchers to get a more detailed look at how genes are expressed in cancer cells, said Katherine Hoadley, PhD, a UNC Lineberger member and research assistant professor in genetics. And she said gene expression analysis has been shown to be “incredibly useful” in classifying multiple tumor types by their molecular characteristics.
“What set the TCGA project apart from similar genomic projects is that we actually had six different, very diverse and broad-reaching genome analysis technologies that we could use to study tumors’ molecular characteristics,” said Charles M. Perou, PhD, a UNC Lineberger member and professor of genetics and pathology in the UNC School of Medicine. “By handling much of the project’s RNA sequencing, UNC played a major role in making that comprehensive approach to the genetic characterization of tumors possible.”
TCGA has resulted in multiple publications and findings, with 10 studies in the journal Nature, three in the journal Cancer Cell, and three in the journal Cell. UNC researchers played prominent roles in all of these studies, including being the lead site for TCGA studies of breast cancer and glioblastoma, the most common form of malignant brain cancer in adults. Perou and Hoadley led a recent study published in Cell that pointed to a new molecular classification for cancers. For that paper, the researchers studied 12 different tumor types at once.
The research that the sequencing helped to inform as part of TCGA helped push the field of cancer genomics to the next level, Hayes said.
“Before, there was always the promise of sequencing – that it could do this, it might reveal that,” Hayes said. “And although not all the data is analyzed yet from this effort, I think we’ve moved past the theoretical questions about what we might find, and into a much more real state of here is what the cancer genome looks like.”
And while the production side of the project is done, Hoadley said researchers plan to continue to use the data for further analysis. In addition, said the TCGA model is expected to be used for future collaborative cancer research projects. Major findings from TCGA will be reviewed at an upcoming symposium to be hosted by UNC Lineberger April 8-9 at The William and Ida Friday Center for Continuing Education.
About UNC Lineberger
One of only 41 NCI-designated comprehensive cancer centers, the University of North Carolina Lineberger Comprehensive Cancer Center brings together some of the most exceptional physicians and scientists in the country to investigate and improve the prevention, early detection and treatment of cancer. With research that spans the spectrum from the laboratory to the bedside to the community, UNC Lineberger faculty work to understand the causes of cancer at the genetic and environmental levels, to conduct groundbreaking laboratory research, and to translate findings into pioneering and innovative clinical trials. For more information, please visit www.unclineberger.org.