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Cancer Categories Recast in Largest-Ever Genomic Study

Research Suggests One in 10 Patients Could Be Classified Differently, and Perhaps Receive Different Treatments

By Pete Farley    |   UCSF.edu | August 7, 2014

Cancer Categories Recast in Largest-Ever Genomic Study

DNA molecule unwinding from a chromosome inside the nucleus of a cell. Courtesy of the National Humane Genome Research Institute.

New research partly led by UC San Francisco-affiliated scientists suggests that one in 10 cancer patients would be more accurately diagnosed if their tumors were defined by cellular and molecular criteria rather than by the tissues in which they originated, and that this information, in turn, could lead to more appropriate treatments.

In the largest study of its kind to date, scientists analyzed molecular and genetic characteristics of more than 3,500 tumor samples of 12 different cancer types using multiple genomic technology platforms.

HDFCCC contributors:
-Christina Yau and Denise Wolf (with Breast Oncology Program) were main investigators on the classification (both co-first author)
-Christopher Benz  is a member of the TCGA steering group
-Laura van ’t Veer and Eric Collisson participated as co-investigators in this specific TCGA study.


Cancers traditionally have been categorized by their "tissue of origin"—such as breast, bladder, or kidney cancer. But tissues are composed of different types of cells, and the new work indicates that in many cases the type of cell affected by cancer may be a more useful guide to treatment than the tissue in which a tumor originates.

The study, published August 7, 2014 in the online edition of Cell, was conducted as part of The Cancer Genome Atlas (TCGA) initiative spearheaded by the National Cancer Institute and National Human Genome Research Institute, both part of the National Institutes of Health.

In the national media

The San Francisco Chronicle (8/8, Colliver, 2.87M) reports that research published in Cell suggests that “classifying cancer tumors by their molecular structure rather than the tissue or organ where they were found, such as the breast or bladder, may lead to more accurate diagnoses and potentially better treatments and outcomes for patients.” Investigators, “in the largest undertaking to analyze and compare different cancer types based on genomic sequencing...found at least 10 percent of tumors – and possibly as high as 30 to 50 percent – would be identified differently if oncologists determined their diagnoses by a tumor’s molecular makeup.” The Chronicle notes, “The project is part of a national effort, the Cancer Genome Atlas project, which started in 2006 and is funded by the National Institutes of Health.”

        The Los Angeles Times (8/8, Rosen, 3.42M) reports that the investigators “hope the patterns revealed in their results will eventually translate into tangible benefits for cancer patients.” In order “to accelerate this, they have made all their results available in a publicly searchable archive.”

        The Marin (CA) Independent Journal (8/8, Halstead, 82K) reports that the investigators “performed a molecular analysis of 12 different tumor types and ‘generally came up with three to five subtypes for each of the cancers, whether it was lung cancer, colon cancer, head-neck cancer, breast cancer, or brain cancer,’ said Christopher Benz, a principal investigator at the Buck Institute who contributed to the study.”

        Newsweek (8/8, 105K) reports, “Of the 12 cancer subtypes they discovered, five correlated with traditional tissue-of-origin categorizations.” However, the others “were previously unidentified subtypes that affected more than one kind of tissue, for which the old classification system wouldn’t apply.” For example, “results identified at least three different kinds of bladder cancer.”

        HealthDay (8/8, Preidt, 5K) reports that among other things, the investigators “confirmed known differences between two forms of breast cancers called basal-like and luminal.” However, “they also discovered that these differences are significant and that basal-like breast cancers – commonly referred to as triple-negative – are a distinct class of tumor.”

Medscape (8/8, Castellino, 192K) also covers the story.

In the new work, TCGA Research Network scientists analyzed DNA, RNA, and protein from 12 tumor types using six different genomic technologies to see how different tumor types compare to one another. The team arrived at a classification based on 12 cancer subtypes. Five of these matched up well with tissue-of-origin classifications, but several newly identified subtypes were seen to affect a variety of tissues.

"This genomic study not only challenges our existing system of classifying cancers based on tissue type, but also provides a massive new data resource for further exploration, as well as a comprehensive list of the molecular features distinguishing each of the newly described cancer classes," said co-senior author Christopher Benz, MD, professor at the Buck Institute for Research on Aging, adjunct professor of medicine at UCSF, and a member of UCSF’s Helen Diller Family Comprehensive Cancer Center.

Particularly striking results were seen in bladder and breast cancers. At least three different subtypes of bladder cancer were identified, one virtually indistinguishable from lung adenocarcinomas, and another most similar to squamous-cell cancers of the head and neck and of the lungs. (In the new study, these squamous-cell cancers appeared to form their own subtype, whether they originated in the lungs or in the head and neck.) The findings may help explain why patients with bladder cancer "often respond very differently when treated with the same systemic therapy for their seemingly identical cancer type," said Benz.

The study also confirmed known differences between subtypes of breast cancer known as "basal-like" and "luminal" cancers. But because the researchers compared these cancers not just with one another but with many other types of cancer, they were able to reveal that these differences are quite profound, and that basal-like breast cancers constitute their own distinct class. "What’s amazing is that basal breast cancer is as different from luminal breast cancer as it is from, say, kidney cancer," said co-lead author Denise Wolf, PhD, a research scientist based in UCSF’s Department of Laboratory Medicine.

Commonly referred to as "triple-negative," basal-like cancers are particularly aggressive and are more prevalent among African-American women and younger women. "Even though these basal-like cancers arise in the breast, on the molecular level they have more in common with ovarian cancers and cancers of squamous-cell origin than with other subtypes of breast cancer," said co-lead author Christina Yau, PhD, a staff scientist at the Buck Institute and assistant professor of surgery at UCSF.

TCGA was launched in 2006 with the goal of compiling genomic atlases of more than 20 types of cancer. As the project proceeded, however, commonalities across cancer types began to emerge, which led to the creation of the TCGA "Pan-Cancer" project, the source of the data used in the new study.

 

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