The 2015 ITOG International Meeting was recently held in Rome, Italy, where Dr. Thomas Giordano presented the lead talk on a new comprehensive analysis of thyroid cancer from The Cancer Genome Atlas (TCGA) Research Network, a federally funded project to elucidate the molecular characterization of various cancer types. Dr. Giordano’s findings are extremely important to the thyroid cancer community and will potentially change the way thyroid cancers are classified and diagnosed. Further, the identification of new markers of aggressive tumors could allow for better targeting of tailored treatments to individual patients.

Thyroid cancer incidence has increased three-fold over the last 30 years. While the tumors are often slow-growing and easily treated with a combination of surgery, radioactive iodine, and thyroid hormone, a subset of patients will develop more aggressive and deadly thyroid cancers. Until recently, the classification of papillary thyroid carcinoma (PTC) as benign or malignant relied on surgery to remove some or all of a patients’ thyroid, even if there was an 80% chance that the cancer would not develop.

Dr. Giordano, Professor of Pathology at the University of Michigan Medical School, was the project co-lead for TCGA thyroid cancer analysis along with Dr. Gad Getz, director of Cancer Genome Computational Analysis at the Broad Institute of MIT/Harvard. In this study, published in Cell, October 2014, the authors performed a comprehensive molecular characterization of papillary thyroid carcinomas from 496 patient samples to identify all of the genetic mutations that play a role in cancer progression. They found several new cancer drivers, as well as new variations of existing genes and, in doing so, identified markers of aggressive tumors.

One interesting observation from the study is that the thyroid cancer genome is relatively “quiet”, with fewer genetic mutations than in other common cancers, possibly explaining why the disease is generally slow to progress. Fewer mutations enabled researchers to highlight the key signaling pathways involved in driving thyroid tumors. Prior to this study, the percentage of PTC with no known oncogenic drivers was approximately 25%, making diagnosis and treatment relatively broad in scope. This exhaustive approach uncovered the genetic drivers of more of these cancers, whittling the number of unknown genetic drivers down to 3.5 percent.

The oncogenic drivers can be pared down to two primary groups: BRAF V600E and RAS mutant-PTCs. Interestingly, within these two primary groups, in particular the BRAF group, numerous different subtypes of thyroid cancer exist. To date, thyroid cancers associated with BRAF, for example, had been grouped in the same category, yet this study revealed additional layers of genetic diversity and found that certain subtypes of BRAF-mutated thyroid cancers are associated with higher risk and less differentiated cancers.

This impressive study described the genomic landscape of thyroid cancer at a refined molecular level and will serve as a springboard for critical discussions in the thyroid community. One initial recommendation is for researchers and pathologists to consider reclassifying thyroid cancer based on molecular signatures to better reflect their underlying behavior. Reclassifying the disease based on genetic markers, while difficult, could situate thyroid cancer patients to benefit from more precision-based therapies. This new information will also help physicians separate those patients who need aggressive treatment from those whose tumor is never likely to grow or metastasize. This diagnostic refinement could have widespread impact as a large number of patients receive indeterminate diagnoses on their nodules each year.