Molecular profiling of sporadic medullary thyroid carcinomas - a next-generation sequencing-based study

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Medullary thyroid carcinomas (MTCs) comprise 75% sporadic and 25% hereditary forms.
• Understanding the molecular landscape of sporadic MTC (sMTC) is crucial for diagnosis and treatment.

Purpose of the Study:

• To determine histopathological parameters and molecular alterations in sMTC.
• To identify potential therapeutic targets and prognostic markers in sMTC using targeted next-generation sequencing (NGS).

Main Methods:

• Targeted next-generation sequencing (NGS) of 62 genes was performed on sMTC samples.
• Analysis included histopathological parameters and molecular changes.
• Artificial intelligence was used to identify potential genes of interest.

Main Results:

• All identified RET mutations were missense mutations.
• Pathogenic mutations in EIF1AX, HRAS, MAP3K1, and KDR were observed.
• Mutations associated with nodal metastasis and tumor progression were identified, irrespective of RET mutation status.
• A patient with advanced disease and an EIF1AX mutation experienced liver metastasis and died within 25 months.

Conclusions:

• NGS findings can guide therapeutic strategies for advanced-stage sMTC with metastatic disease.
• Mutations in HRAS, MAP3K1, and EIF1AX may have prognostic significance in sMTC.
• Further studies with larger cohorts are needed to incorporate these findings into treatment guidelines.