Following the Chernobyl nuclear accident, children exposed to radioactive iodine fallout developed thyroid cancers at greatly increased rates. The molecular hallmark of these radiation-associated thyroid tumors is:

• A Point mutation in BRAF V600E
• B PAX8-PPAR gamma translocation
• C RAS codon 61 point mutation
• D RET/PTC chromosomal rearrangement ✓

Explanation

Ionizing radiation induces double-strand DNA breaks that are misrepaired as chromosomal inversions and translocations. In radiation-associated papillary thyroid carcinoma, this produces RET/PTC fusions, formed when the RET tyrosine kinase domain fuses to a heterologous promoter region such as PTC1 (involved with H4) or PTC3. These fessions activate MAPK constitutively. BRAF V600E point mutations characterize sporadic adult papillary carcinoma, and RAS mutations mark follicular lesions, making them the discriminating distractors.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.