Incremental value of expanded mutation panel when used in combination with microRNA testing in indeterminate thyroid nodules

  • Purpose: We describe our experience with mutation and microRNA (miRNA) classifier testing of indeterminate thyroid nodules, reporting incremental value of an expanded mutational panel when used in combination with miRNA classification.

    Methods: Two cohorts of indeterminate nodules received combination mutation and miRNA testing. The first (n=5899) underwent focused mutation panel testing (ThyGenX®) targeting common strong and weak driver mutations. The second (n=2214) received an expanded mutation panel (ThyGeNEXT®) including the same mutations in the focused panel plus additional mutations in 5 cancer genes and 35 translocations. Negative, positive, and strong positive miRNA results were correlated to mutation results.

    Results: The expanded panel increased the number of nodules that had strong driver mutations by 5%, weak driver mutations by 14% and reduced the number of nodules that lacked mutations by 19%. The presence of strong driver mutations was highly correlated with positive miRNA results, with 97% of such nodules having positive results, 90% of which were strong positive. The majority of mutations detected were weak drivers, with 49% having negative miRNA results and only 13% having strong positive results. Only 7% of nodules that lacked mutations had positive miRNA results, 24% of which were strong positive.

    Conclusion: Expansion of the panel detected additional mutations with the majority being weak drivers of cancer. Consistently, half of these nodules had miRNA results associated with benign biology. Some nodules with weak driver mutations and some lacking mutations had miRNA results highly associated with strong driver mutations, elevating concern for cancer above that determined by mutation analysis alone.


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