The Asco Post

Largest Cancer Genetic Analysis Reveals New Way of Classifying Cancer

By The ASCO Post
Posted: 8/7/2014 3:34:43 PM
Last Updated: 8/7/2014 3:34:43 PM

Key Points:
  • In the largest, most diverse tumor genetic analysis ever conducted, researchers found that cancers are more likely to be genetically similar based on the type of cell in which the cancer originated, rather than the type of tissue.
  • The new approach may shift how cancer drugs are developed, focusing more on the development of drugs targeting larger groups of cancers with genomic similarities.

Researchers with The Cancer Genome Atlas (TCGA) Research Network have completed the largest, most diverse tumor genetic analysis ever conducted, revealing a new approach to classifying cancers. The work, published in Cell, not only revamps traditional ideas of how cancers are diagnosed and treated, but could also have a profound impact on the future landscape of drug development.

“We found that 1 in 10 cancers analyzed in this study would be classified differently using this new approach,” said Chuck Perou, PhD, Professor of Genetics and Pathology, at the UNC Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill and senior author of the paper. “That means that 10% of the patients might be better off getting a different therapy—that’s huge.”

Since 2006, much of the research has identified cancer not as a single disease, but as many types and subtypes; these disease types are defined based on the tissue in which it originated. In this scenario, treatments were tailored to which tissue was affected, but questions have always existed because some treatments work, and fail for others, even when a single tissue type is tested.

Study Details

In their work, TCGA researchers analyzed more than 3,500 tumors across 12 different tissue types to see how they compared to one another—the largest data set of tumor genomics ever assembled, explained Katherine Hoadley, PhD, Research Assistant Professor in Genetics at UNC Lineberger and lead author. They found that cancers are more likely to be genetically similar based on the type of cell in which the cancer originated, compared to the type of tissue in which it originated.

“In some cases, the cells in the tissue from which the tumor originates are the same,” said Dr. Hoadley. “But in other cases, the tissue in which the cancer originates is made up of multiple types of cells that can each give rise to tumors. Understanding the cell in which the cancer originates appears to be very important in determining the subtype of a tumor and, in turn, how that tumor behaves and how it should be treated.”

Drs. Perou and Hoadley explain that the new approach may also shift how cancer drugs are developed, focusing more on the development of drugs targeting larger groups of cancers with genomic similarities, as opposed to a single tumor type as they are currently developed.

Basal-Like Breast Cancer

One striking example of the genetic differences within a single tissue type is breast cancer. The breast gives rise to multiple types of cancer—luminal A, luminal B, HER2-enriched, and basal-like—which was previously known. In this analysis, the basal-like breast cancers looked more like ovarian cancer and cancers of a squamous-cell type origin rather than other cancers that arise in the breast.

“This latest research further solidifies that basal-like breast cancer is an entirely unique disease and is completely distinct from other types of breast cancer,” said Dr. Perou. In addition, bladder cancers were also quite diverse and might represent at least three different disease types that also showed differences in patient survival.

As part of the Alliance for Clinical Trials in Oncology, a national network of researchers conducting clinical trials, UNC researchers are already testing the effectiveness of carboplatin in addition to standard chemotherapy for patients with triple-negative breast cancer, of which 80% are the basal-like subtype. The results of the CALGB 40603 study were just published in the Journal of Clinical Oncology and showed a benefit of carboplatin in triple-negative breast cancer patients, suggesting that there may be great value in comparing clinical results across tumor types that share common genomic similarities.

Dr. Perou, Christopher C. Benz, MD, of the Buck Institute for Research on Aging, and Joshua M. Stuart, PhD, of the University of California, Santa Cruz, are the corresponding authors for the Cell article.

The study was supported in part by grants from the National Institutes of Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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