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Genomic Study Changes Cancer Categories

Findings could lead to more effective treatments

New research partly led by scientists at the University of California–San Francisco 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, the researchers analyzed the molecular and genetic characteristics of more than 3,500 tumor samples of 12 different cancer types using multiple genomic technology platforms. 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 research 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 findings were published online August 7 in Cell.

Scientists analyzed DNA, RNA, and protein from 12 tumor types using six different genomic technologies to see how different tumor types compare with 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 found 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.

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,” Benz said.

The study also confirmed known differences between subtypes of breast cancer known as “basal-like” and “luminal” cancers. 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.

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 another co-author, Christina Yau, PhD.

Benz thinks the number of patients eligible for reclassification will swell when more tumor samples and additional tumor types are included in the project’s next round of analysis, which is expected to include more than 20 different tumor types. “We’re just appreciating the tip of the iceberg when considering the potential of this multi-platform type of genomic analysis,” he said. “It could be that as many as 30 or 50 percent of cancers need to be reclassified.”

Source: UCSF; August 7, 2014.

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