A research network in the US proposes that cancer should be classified according to genetic and molecular features rather than by the type of tissue in which the tumor arises. While more work is needed to confirm and build on findings that look set to rewrite oncology textbooks, the scientists say such a system would be better for patients because it would help tailor treatment to their individual needs.
Writing about their findings in the journal Cell, researchers from The Cancer Genome Atlas (TCGA) describe how they analyzed more than 3,500 tumors on multiple genomic technology platforms.
There have already been studies that suggest cancer should be defined by features at the genetic and molecular level. For example, Medical News Today recently reported another TCGA study that found four distinct molecular subtypes of stomach cancer.
But in this latest study – the largest genomic study of cancer – the researchers found even across tissue types (for instance, breast, bladder and kidney), what we currently regard as different cancers have tumors that are more similar at the molecular and genetic level than at the tissue level.
In explaining the impact of the findings, co-corresponding author Chris Benz, a professor at the Buck Institute for Research on Aging in Novato, CA, points out most of our tissues comprise many different types of epithelial and non-epithelial cells (epithelial cells being those that line cavities in the body and cover flat surfaces, while non-epithelial cells form other tissue types such as connective, muscle and nervous tissue), and:
“This disruptive 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.”
He cites the example of bladder cancer, which they propose should be reclassified into several different types, each with distinct and different outcomes, to explain why patients can expect quite different results when treated with the same systemic therapy.
For the study, the scientists compared the DNA, RNA and proteins of 3,527 specimens of 12 different tumor types by analyzing them with six different “platform technologies.” The results showed tumors were more likely to be molecularly and genetically similar based on their cell type of origin as opposed to their tissue type of origin.
For example, the study suggests there are at least three different subtypes of bladder cancer, one of which is almost identical to lung adenocarcinoma, and another that is similar to squamous cell cancers found in the head-and-neck and lungs.
The study also confirms known differences in subtypes of breast cancer but reveals a surprising finding in that basal-like breast cancers – also known as triple-negative breast cancer – are actually a class of their own. These cancers are very aggressive and more common in African-American and younger women.
Even though these basal-like cancers may arise in the breast, the study shows that at the molecular level they are more like ovarian cancers and cancers of squamous cell origin than other breast cancer subtypes.
The team says the findings suggest at least 1 in 10 cancer patients would receive a different classification of their cancer type under the new system. However, Prof. Benz believes this proportion will grow after the next round of analysis, which will look at more samples and tumor types.
He anticipates this will show over 20 types of tumor, based on classification by molecular and genetic features at the cell level:
“We’re just appreciating the tip of the iceberg when considering the potential of this multi-platform type of genomic analysis. It could be that as many as 30 or 50% of cancers need to be reclassified.”
He believes this study and future repeats will improve design of clinical trials by helping to identify patients more likely to respond to new treatments based on the genomic reclassification of their tumors. He notes:
“Although follow-up studies are needed to validate and refine this newly proposed cancer classification system, it will ultimately provide the biologic foundation for that era of personalized cancer treatment that patients and clinicians eagerly await.”