Category | Subtype/Details | Genetic Alterations | Notes / Associations |
Histologic Subtype Associations | Tall Cell PTC | - BRAF p.V600E (80%) - TERT promoter mutations | High prevalence of BRAF p.V600E; some cases show TERT mutations |
Follicular Variant PTC | - RAS mutations - RET, NTRK, ALK fusions | RAS mutations common; presence of various gene fusions |
Oncocytic PTC | - BRAF mutations - GRIM-19 - RET rearrangements | Diverse genetic profile including BRAF and RET rearrangements |
Warthin-like PTC | - BRAF p.V600E | Predominantly associated with BRAF p.V600E |
Radiation-Associated PTC | Solid/Trabecular PTC | - NCOA4::RET rearrangements | Common in radiation-associated cases |
Non-Radiation-Associated Cases | - CCDC6::RET - NCOA4::RET - ETV6::NTRK3 fusions | Diverse fusions; RET fusions linked to radiation exposure |
RET fusions strongly associated with radiation exposure (e.g., Chernobyl) |
Other Genetic Alterations | - CTNNB1 mutations - p53 mutations - Chromosome 1 LOH | CTNNB1 in fibromatosis-like variants; p53 and LOH in Tall Cell PTC |
TERT Promoter Mutations | - C228T (NC_000005.9:g.1295228G>A) - C250T (NC_000005.9:g.1295250G>A) | Found in ~10% of PTC; associated with poor prognosis and often coexists with BRAF p.V600E |
Less Common Mutations & Fusions | - Mutations: HRAS, KRAS, PPM1D, CHEK2, MEK1 - Fusions: BRAF, PPARG, THADA, LTK, MET, FGFR2 - NTRK1, NTRK3 fusions (3-5%) | NTRK fusions are rare but actionable targets for therapy |
RET Fusions | - CCDC6::RET (60-70% in sporadic PTC) - NCOA4::RET (20-30%) | Common in sporadic and radiation-induced PTC; more prevalent in pediatric cases |
Copy Number, Gene Expression, & microRNA | - Various alterations reported | Contribute to PTC tumorigenesis but are less well understood |
Familial PTC | Syndromic | - APC mutations (e.g., Familial Adenomatous Polyposis - FAP) | Associated with syndromic forms of PTC |
Non-Syndromic | - Genetic basis poorly understood | Genetic predisposition remains an area of ongoing research |
RAS mutations & rare BRAF p.K601E seen in follicular patterned tumors | | Histologic Subtype Associations | - Tall cell PTC: High BRAF p.V600E (80%), some cases show TERT promoter mutations
Follicular variant PTC: RAS mutations, some show RET, NTRK, ALK fusions
Oncocytic PTC: Can have BRAF mutations, GRIM-19, and RET rearrangements
Warthin-like PTC: BRAF p.V600E | Different mutations correlate with histologic subtypes and aggressiveness | | Radiation-Associated PTC | - Solid/trabecular PTC: Commonly harbors NCOA4::RET rearrangements
Non-radiation-associated cases: CCDC6::RET, NCOA4::RET, ETV6::NTRK3 fusions | RET fusions are strongly associated with radiation exposure (e.g., Chernobyl-associated PTC) | | Other Genetic Alterations | - CTNNB1 mutations (spindle cells in PTC with fibromatosis-like stroma)
p53 mutations, Chromosome 1 LOH (Tall Cell PTC) | CTNNB1 mutations seen in rare fibromatosis-like variants | | TERT Promoter Mutations | - C228T (NC_000005.9:g.1295228G>A)
C250T (NC_000005.9:g.1295250G>A) | Found in ~10% of PTC
Associated with poor prognosis and aggressive behavior
Often coexists with BRAF p.V600E | | Less Common Mutations & Fusions | - Mutations in HRAS, KRAS, PPM1D, CHEK2, MEK1
Fusions in BRAF, PPARG, THADA, LTK, MET, FGFR2
NTRK fusions (NTRK1, NTRK3) (3-5%) | NTRK fusions are rare but actionable targets for therapy | | RET Fusions | - CCDC6::RET (most common in sporadic PTC, 60-70%)
NCOA4::RET (20-30%)
Common in radiation-induced PTC | RET rearrangements are more common in pediatric and radiation-associated cases | | Copy Number, Gene Expression, & microRNA | Alterations reported | Contribute to PTC tumorigenesis but less well understood | | Familial PTC | - Syndromic: APC mutations (e.g., FAP)
Non-syndromic: Poorly understood genetic basis | Genetic predisposition remains an area of ongoing research |
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