Papillary thyroid carcinoma (PTC) is most commonly associated with which chromosomal rearrangement?

Explanation

## Chromosomal Rearrangements in Papillary Thyroid Carcinoma **Key Point:** The question specifically asks about **chromosomal rearrangements** in PTC. RET/PTC rearrangement is the most well-known and classic chromosomal rearrangement associated with papillary thyroid carcinoma, occurring in 10–20% of sporadic cases and up to 50–80% of radiation-induced PTCs. ### Molecular Alterations in PTC — Classification by Type | Genetic Alteration | Frequency | Type | Notes | | --- | --- | --- | --- | | BRAF V600E | 30–70% | **Point mutation** (NOT a rearrangement) | Most common genetic alteration overall | | RET/PTC rearrangement | 10–20% (sporadic); up to 80% (radiation-induced) | **Chromosomal rearrangement** | Most common rearrangement in PTC | | PAX8-PPARG | 2–5% | Translocation t(2;3) | More common in follicular carcinoma | | TP53 mutation | <5% | Point mutation | Associated with anaplastic transformation | **High-Yield Distinction:** - **BRAF V600E** is the most common *genetic alteration* overall in PTC, but it is a **point mutation**, not a chromosomal rearrangement. - **RET/PTC rearrangement** involves fusion of the RET proto-oncogene (chromosome 10q11) with various partner genes (most commonly H4/D10S170 in RET/PTC1, or ELE1/RFG in RET/PTC3), resulting in constitutive activation of the RET tyrosine kinase. This is a true **chromosomal rearrangement**. - **PAX8-PPARG** translocation t(2;3)(q13;p25) is a chromosomal rearrangement but is more characteristic of follicular thyroid carcinoma, not PTC. ### Why RET/PTC is the Answer The stem explicitly asks for a **chromosomal rearrangement**. BRAF V600E (option C), while the most common genetic alteration in PTC overall, is a single nucleotide point mutation — not a chromosomal rearrangement. TP53 mutation (option D) is also a point mutation. PAX8-PPARG (option B) is a rearrangement but is characteristic of follicular carcinoma. RET/PTC rearrangement (option A) is the most common true chromosomal rearrangement specifically associated with PTC. **Clinical Pearl:** RET/PTC rearrangements are particularly prevalent in radiation-exposed patients (e.g., post-Chernobyl pediatric PTC cases), making them a classic exam association. RET/PTC3 is more common in radiation-induced PTC, while RET/PTC1 predominates in sporadic cases. **Mnemonic:** **RET/PTC = Rearrangement in PTC** — when the question says "rearrangement," think RET. [cite: Robbins & Cotran Pathologic Basis of Disease, 10e, Ch 24; Williams Textbook of Endocrinology]