The following is a summary of “Next-Generation Sequencing in Sporadic Medullary Thyroid Cancer Patients: Mutation Profile and Disease Aggressiveness,” published in the April 2024 issue of Endocrinology by Shirali, et al.

Next-generation sequencing (NGS) analysis has enhanced the detection of somatic mutations in sporadic medullary thyroid carcinoma (sMTC), including RET M918T, previously considered a negative prognostic indicator. For a study, researchers sought to investigate the association between clinicopathologic behavior and somatic mutations identified through clinically motivated NGS in sMTC.

The retrospective cohort study analyzed patients with sMTC who underwent NGS for treatment planning. Clinicopathologic factors, time to distant metastatic disease (DMD), disease-specific survival (DSS), and overall survival (OS) were compared across different somatic mutations.

Somatic mutations were detected in 191 sMTC tumors, including RET M918T (53.4%), other RET codons (10.5%), RAS (18.3%), somatic RET indels (8.9%), and RET/RAS wild-type (WT) status (8.9%). Patients’ median age at diagnosis was 50 years (range, 11-83); 46.1% were female. No significant differences were observed in sex, TNM category, systemic therapy use, time to DMD, DSS, or OS when comparing patients with RET M918T, RET-Other, and RET WT (including RAS and RET/RAS WT). Multivariate analysis revealed that older age at diagnosis (HR 1.05, P < .001; HR 1.06, P< .001) and M1 stage at diagnosis (HR 3.17, P = .001; HR 2.98, P = .001) were associated with decreased DSS and OS, respectively, but mutation cohort was not. Similarly, there was no significant difference in time to DMD, DSS, or OS between RET M918T and RET indels.

Somatic RET mutations identified through clinically motivated NGS did not appear to impact DSS or OS in patients with sMTC.

Reference: academic.oup.com/jes/article/8/6/bvae048/7657108