Study improves understanding of genetic drivers of thyroid cancer

A comprehensive analysis of the genomes of nearly 500 papillary thyroid carcinomas (PTC) – the most common form of thyroid cancer – has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive disease development. The findings also may help improve diagnosis and treatment. Investigators with The Cancer Genome Atlas (TCGA) Research Network identified new molecular subtypes that will help clinicians determine which tumours are more aggressive and which are more likely to respond to certain treatments. Their findings confirmed that PTCs are driven primarily by mutations in one of two cancer-associated genes: BRAF (and a particular mutation, V600E) or RAS. The work also detailed many differences between the two genetic types, particularly in signalling pathways that promote tumour development and growth.

The researchers developed a scoring system to reflect gene expression in the two PTC types, allowing them to characterize tumours and determine both the pathway a tumour uses to send signals and its relative aggressiveness. Where a tumour lies on a scale – called its thyroid differentiation score – can have important treatment implications because different tumor signaling properties can mean the cancer responds differently to particular therapies.

The study also showed that BRAF-driven tumors have a broader range of genetic complexity than previously thought, with distinct subtypes. The results suggest a need for a new classification system that more accurately reflects underlying genetic characteristics of the cancer.

Thyroid cancer is the fastest growing cancer in the United States, with more than 20,000 new PTC cases each year. Most thyroid cancers are slow-growing and treatable with surgery, hormone therapy and radioactive iodine. National Human Genome Research Institute