How The Cancer Genome Atlas Will Shape the Future of Cancer Research

A decadelong effort to genomically characterize multiple cancers begets a huge archive: 33 cancer types, 11,000 tumors and 27 new papers that explain the findings.

12:00 PM

Author | Rosemary Clandos

Thirteen years after its initial funding, The Cancer Genome Atlas (TCGA) has analyzed 2.5 petabytes of data representing 33 different types of cancer.

That's no small feat: One petabyte has the storage capacity of 212,000 DVDs.

MORE FROM THE LAB: Subscribe to our weekly newsletter

The project has created thorough, multidimensional maps of the key genomic changes in both common and rare cancers.

Now, a series of 27 papers publishing across the Cell Press family of journals summarizes its final project, PanCancerAtlas, the most comprehensive cross-cancer genomic analysis available.

"Nearly all TCGA projects identified previously unrecognized molecular subgroups, and moreover, genomic insights from some projects (e.g., thyroid cancer) have catalyzed significant revisions to how we categorize some cancers," says Thomas Giordano, M.D., Ph.D., Henry Clay Bryant professor of pathology at Michigan Medicine. Giordano has served as a member of the PanCancerAtlas steering committee, and he co-led the projects on thyroid and adrenal cancer.

The University of Michigan has contributed tumor samples and led several TCGA projects. Participating faculty include David Beer, Ph.D., who contributed to the esophageal cancer project, and Thomas Carey, Ph.D., who contributed to the head and neck squamous cell carcinoma project.

Giordano discussed the project and its implications:

What were the goals for TCGA and what can we take away from it?

Giordano: For the 10-year project, there were three primary goals: to better understand the molecular underpinnings of cancer, to derive original molecular taxonomies, and to identify novel molecular therapeutic targets.

We learned a great deal about the molecular basis of cancer and discovered new mutations, which helped improve molecular diagnostics. The research helped us understand the functional consequences of specific mutations, particularly how they drive the biology of tumors. Nearly all projects identified three to five molecular subgroups of cancer, some of which had not been previously recognized.

SEE ALSO: International Collaboration Leads to Clues About Rare Cancer

For example, in papillary thyroid cancer, two mutations involving proteins in the same signaling pathway were believed to be essentially functionally equivalent. But our data revealed different signaling properties. Understanding this impacts tumor classification, which affects patient care and treatment.

As a pathologist, it's been exciting to understand the underlying genomics and correlate the findings with the microscopic appearance of tumors.

With the thyroid cancer project, we were concerned that the project might be uninteresting because it was focused on the most indolent type of thyroid cancer and excluded the most clinically aggressive types. However, we learned so much about thyroid cancer from that project and it provided a foundation for comparison with other projects.

Now, when researchers study an aggressive type of thyroid cancer, they can compare their results to TCGA and derive increased understanding by that comparison. This holds true for other types of cancer as well

Can you talk about the size and scope of the project?

Giordano: TCGA built a standardized platform for the genomic characterization of cancer. Thirty-three cancer types were examined; 23 were common cancers and 10 were rare. A total of 11,000 tumor types were studied.

One of the rare cancer projects was on adrenocortical cancer. The TCGA project was hesitant to address adrenal cancer because it is so rare, but my colleague Gary Hammer, M.D., Ph.D., director of the endocrine oncology program at U-M, and I were instrumental in making that happen. We assembled an international collaboration to study enough tumors.

We were able to identify three prognostic subgroups, which is a true advance for the field. Now we're trying to translate those findings to the clinic and tailor patient care to the biology of these tumors.

How did the discoveries impact the classification of tumors?

Giordano: It changes the way pathologists think about cancer and re-examines the proper classification of these tumors. When tumor morphology was integrated with genomic features and molecular subtypes, knowledge increased. Insights about genomics for thyroid cancers and other cancers have catalyzed or accelerated revisions of tumor taxonomies, or how we classify tumors.

Thomas Giordano, M.D., Ph.D: "There's a paradigm shift underway and it relates to the transition to precision pathology."

What problems were uncovered by the new cancer taxonomy?

Giordano: Tumors are routinely classified based on what pathologists see through the microscope. However, two tumors that look similar might have different underlying genetic abnormalities, which can only be revealed by molecular pathology.

Fully understanding the genetic landscape in a given tumor type advances molecular pathology testing and informs therapeutic decisions. Instead of treating people with nonspecific chemotherapies, we are undergoing a paradigm shift to using molecularly targeted therapies.

SEE ALSO: How U-M's Genetic Research Bank Fuels Precision Health Work

This will fundamentally change how patients are treated. As we move toward more precision therapy, some patients with specific genetic alterations will respond to drugs. Therapy that works on one mutation won't work on another.

What are some of the challenges moving forward?

Giordano: The main challenge is that genomic characterization of cancer is outpacing development of targeted therapeutics. Some frequently mutated genes are still difficult to target. So we may know the alterations, but we haven't found drugs to block the alterations.

A number of pathways are so difficult to target that some pharmaceutical companies have de-emphasized drug development for those pathways.

What were some of the limitations of the research?

Giordano: TCGA didn't do research on all types of cancer, but the research will be used for comparison and discoveries for many years.

How might these findings affect future research?

Giordano: There's a paradigm shift underway and it relates to the transition to precision pathology. For example, you don't treat lung cancer with traditional chemotherapy until you've determined if there are genetic alterations that can be targeted.

This will be more work for pathologists, but it is exciting work. We will continue to do microscopy, but we'll be doing more and more molecular pathology as we look for actionable genetic alterations.

In the future, results from genomic characterization of tumors will be combined with big data analytics to help guide therapy. Pathologists will be using image analysis and big data combined with insights derived from systems biology and artificial intelligence.

Infographic courtesy of TCGA. Photo by Leisa Thompson.

More Articles About: Lab Report Cancer Research Cancer and Genetics Tumor Registry Cancer: Help, Diagnosis & Treatment
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of health care news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]


Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Featured News & Stories light lights seen on dark navy screen
Health Lab
Researchers identify novel biomarker linked to renal cancer recurrence
Researchers from the University of Michigan Health Rogel Cancer Center have discovered a biomarker that could help identify which renal cancer patients have a higher risk of recurrence.
different cars from helicopter view on highways intersecting going all different ways seeing greenery and roads
Health Lab
Pediatric brain tumors rely on different metabolic “route” to fuel treatment resistance
Researchers at the University of Michigan Health Rogel Cancer Center are one step closer to understanding how pediatric DIPG tumors work.
cancer cell blue yellow
Health Lab
Accessibility issues in cancer care
Researchers at the University of Michigan are finding that many patients may be encountering significant barriers to cancer care, even from their first phone call to a clinic.
white blood cell with some blue on black background artistic looking
Health Lab
White blood cell “nets” could be early warning sign of major immunotherapy complication
When white blood cells, meant to protect the body from infection, are overly activated, they eject their DNA into nets, further disrupting the immune system and making patients more likely to develop a potentially severe reaction to immunotherapy.
woman putting something in vial in lab coat and purple gloves, glasses and mask in clinical looking area
Health Lab
Altering cancer treatment dosing could reduce climate impact, study finds
Changing how often a popular cancer therapy is delivered would reduce greenhouse gas emissions and improve environmental impact without decreasing cancer survival, according to a new analysis from researchers at the University of Michigan Health Rogel Cancer Center.
cancer cell blue yellow
Health Lab
Widening inequality seen where cancer clinical trials are available
The availability of clinical trials of new treatments for cancer varies greatly by geography, and a new study shows more socially vulnerable areas have far fewer.