Genomic Research Indicates the Need for Cancer Reclassification

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1 in 10 patients would be more accurately diagnosed if their tumors were defined by cellular criteria.
1 in 10 patients would be more accurately diagnosed if their tumors were defined by cellular criteria.

New genomic research is suggesting that it may be time to reclassify several types of breast and bladder cancers. In the largest study of its kind, researchers analyzed molecular and genetic characteristics of 3,527 specimens from 12 different tumor types.

Using six different genomic technologies, the findings suggest that at least 1 in 10 patients with cancer would be more accurately diagnosed and potentially better treated if their tumors were defined by cellular and molecular criteria instead of tissue of origin.1

“I think the textbooks are going to be rewritten,” said the study's senior coauthor Christopher Benz, MD, who is a professor at Buck Institute for Research on Aging in San Francisco, California. “So there will be a major reclassification that improves upon the idea of describing each tumor by the organ from which it arose and instead it will be based on the molecular characteristics of the cell type generating the tumor within that organ.”

Dr. Benz said these new findings should lead to a complete reorganization of how cancer clinical trials are conducted. He noted that several bladder and breast cancers may need to be immediately reclassified. Dr. Benz and his colleagues found that one type of bladder cancer was virtually indistinguishable from lung adenocarcinomas and another subtype of bladder cancer was very similar to squamous cell cancers of either the lung or the head and neck.

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Overall, the researchers concluded that bladder cancers could be divided into at least three different pan-cancer subtypes.

“With bladder cancer, all current first-line and second-line treatments are given with little recognition that there are multiple bladder cancer subtypes that probably need to be treated very differently,” Dr. Benz told Cancer Therapy Advisor.

Gopal Gupta, MD, who is an assistant professor in the department of urology/surgery at Loyola University in Chicago, Illinois, said this study demonstrates that, at a molecular level, it is possible to correlate pathologic signatures with genetic signatures of the variant histologies. He said that could lead to improved overall outcomes in patients diagnosed with bladder cancer.

“This is overall a remarkable study that demonstrates the power of massive genomics and proteomics,” Dr. Gupta told Cancer Therapy Advisor. “Bladder cancers share close similarity with other cancer types. This study may lead to clinical trials using anticancer drugs commonly used for other malignancies in bladder cancer where there is a paucity of therapies.” 

The latest genomic findings suggest that all cancers can be classified under 11 molecular subtypes. Dr. Benz said this type of pan-cancer analysis will be further extended over the next 2 years to include more than 10,000 different tumors arising from over 20 different organ sites. He said that the new classifications then will likely grow and include additional molecular subtypes.

Under the initial version of this new classification system, the researchers found that five subtypes matched up well with their tissue-of-origin counterparts. However, several distinct cancer types were found to converge into very specific molecular subtypes.

Dr. Benz said with breast cancer the findings produced a new surprise and the findings will likely change clinical practice. “For nearly 15 years we have known that there are four or five different molecular subtypes,” said Dr. Benz. “But to our surprise we found that one of these subtypes (basal-like breast cancer) actually looks more like certain subtypes of lung and ovarian cancers than like any of the other breast cancer subtypes."

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Christopher Corless, MD, PhD, who is a professor of pathology at the Knight Cancer Institute at Oregon Health & Science University in Portland, Oregon, said the affect of the molecular subclassification of cancers is already being observed across many different cancers.

For example, there are a dozen different principle driver mutations in adenocarcinomas of the lung and each one is responsive to a different type of therapy. “What is important about this study is that it uses a novel approach to integrate several different types of molecular data in order to gain new insights into the inner workings of a tumor.

The observation that bladder cancers can be subdivided into at least three very different categories fits well with the diversity that pathologists have long observed in these cancers under the microscope,” Dr. Corless told Cancer Therapy Advisor

Dr. Corless said that the challenge now is to build new clinical tests that can better distinguish these bladder cancer types and then prove that tailoring therapies according to these categories improves patient outcomes. Mateusz Opyrchal, MD, PhD, who is an assistant professor of oncology at Roswell Park Cancer Institute in Buffalo, New York, said this study further reinforces that breast cancers can be divided into separate diseases based on their molecular profiles with the hope of improving outcomes.

“Currently, we distinguish hormone-receptor-positive, HER2-positive, and triple-negative types of breast cancer, distinctions that influence our therapy recommendations. Further molecular classification will help us to refine individualized treatment recommendations for our patients,” said Dr. Opyrchal.

Dr. Opyrchal went on to explain that it is possible that these molecular characterizations will be able to improve the design of clinical trials for breast cancer and other tumor types. He concluded that more accurate patient characterization could significantly improve randomization and the discovery of new and more targeted treatments.


  1. Hoadley KA, Yau C, Wolf DM, et al. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell. 2014;158(4):929-944.

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