Distinctive role of mutations in distant metastatic thyroid cancer.

OBJECTIVE

This study investigated the clinical significance of mutations in patients with distant metastatic follicular cell-derived thyroid cancer (FDTC).

METHODS

This study included 310 Chinese patients with distant metastatic FDTC. We analyzed the interactions between mutations and other gene alterations and compared the clinicopathological characteristics of patients with pathogenic (P) or likely pathogenic (LP) mutations (n=9), other gene alterations (n=253), and no gene alterations (n=37). To compare FDTCs with different drivers, isolated , mutations, and fusions were compared with isolated mutations.

RESULTS

The prevalence of mutations was 6.5% (20/310) in the patient cohort. Among patients with mutations, 45% (9/20) harbored P or LP variants and 55% (11/20) harbored variants of uncertain significance (VUS). The coexistence of mutations and other gene alterations was detected in 65% (13/20) of patients. Compared with VUS, P or LP variants were almost mutually exclusive with early driver alterations (such as ) (11.1% 81.8%, P=0.002) and more coexisted with late-hit events, particularly mutations (44.4% 27.3%, P=0.642). Clinically, compared with the no alteration and other alteration groups, the mutation group exhibited larger primary tumors, higher poorly differentiated thyroid cancer proportion, more extrathyroidal extension, more extrapulmonary metastases, and higher radioactive iodine-refractory proportion (all P<0.05). Cases with isolated mutations differed from those with isolated and fusions in terms of tumor size, poorly differentiated thyroid cancer proportion, and metastatic sites, but were similar to cases with isolated mutations in the high proportion of follicular thyroid cancer, N0, and extrapulmonary metastases.

CONCLUSIONS

Mutation of gene is a non-negligible molecular event and it may represent an aggressive subset of FDTCs. has -like clinical characteristics and -mutant tumors exhibit more aggressive clinical behaviors compared with those with and fusions.