A 40-year-old woman has a thyroid nodule. FNA shows papillary thyroid carcinoma (PTC). The molecular alteration most frequently found in conventional PTC and which drives MAPK pathway activation is:

• A RAS mutation (NRAS codon 61) — found in ~50% of follicular variant PTC
• B RET/PTC1 rearrangement — most common in radiation-induced PTC
• C PAX8-PPARγ fusion — characteristic of follicular thyroid carcinoma
• D BRAF V600E point mutation — found in ~60% of conventional PTC ✓

Explanation

BRAF V600E substitution (valine to glutamate at codon 600) is found in ~60% of conventional papillary thyroid carcinoma, making it the most common single molecular alteration in PTC. BRAF V600E constitutively activates BRAF kinase, which phosphorylates MEK1/2, activating ERK-MAPK proliferation signaling. It is associated with the classic and tall-cell variants of PTC, increased risk of lymph node metastasis, and recurrence. BRAF V600E-positive PTC responds to BRAF inhibitors (vemurafenib) in radioiodine-refractory cases. RET/PTC rearrangements are found in post-radiation and childhood PTC (~20% sporadic).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.