Researchers recommended caution when using gene variant and fusion panels alone to diagnose thyroid cancer, based on findings from recent data that showed molecular alterations associated with thyroid cancer were present in both benign and malignant nodules.

“We found that well-established and more recently discovered molecular alterations that are associated with thyroid cancer were found in both benign and malignant nodules,” Richard T. Kloos, MD, who is senior medical director of the endocrinology department at Veracyte, Inc, said in an email interview with Endocrinology Advisor.

The research was presented at the 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association (ITC/ATA).

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Dr Kloos said that there was a lack of multicenter, prospective clinical trials to determine how the gene variants and fusions could be used to diagnose thyroid cancer.

With The Cancer Genome Atlas (TCGA) Research Network’s work expanding the number of genetic alterations found in papillary thyroid carcinoma, Dr Kloos and colleagues set out to analyze these additional variants and fusions from the TCGA studies as well as from the literature in both cancerous and benign samples.

The researchers used genome-wide next-generation sequencing of RNA to evaluate 88 fine-needle aspiration (FNA) biopsies from patients with thyroid nodules.

The panel of genome alterations included 984 genomic alterations, which consisted of 851 somatic variants from mRNA sequencing and 133 fusions across 524 genes.

They also analyzed 63 tissue samples and 110 FNA biopsies without a histopathology diagnosis.

“Consistent with other studies on DNA-based mutations, gene alterations appeared in only 50% of the cancerous samples,” Dr Kloos said. “At the same time, 20% of the benign thyroid samples harbored gene alterations (80% specificity). Thus, gene alterations did not equal cancer and lack of such alterations did not equal benignity.”

Medullary thyroid carcinoma was the most common mutated malignant subtype, at 75%, followed by papillary thyroid carcinoma, at 47%. The researchers noted 41% of follicular adenoma also had mutations.

“These findings suggest that caution should be exercised in using gene variant and fusion panels on their own to rule out or rule in thyroid cancer,” Dr Kloos said. “We look forward to further exploring how gene alteration data, derived from RNA sequencing, can best be used to improve clinical decision-making.”

Disclosure: Dr Kloos and colleagues are employed by or are equity stakeholders in Veracyte Inc.


  1. Kloos RT, Pagan M, Travers K, et al. Short Oral Communication 499. Oncogenic Mutations in Thyroid Carcinoma and Their Power to Detect Malignancy in Diverse Thyroid Neoplasms. Presented at: 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association (ITC/ATA); October 18-23, 2015; Lake Buena Vista, Florida.