Nodule-Specific NRF2-Targeted Upregulation in Patients With KEAP1 Mutations and Familial Nontoxic Multinodular Goiter
Authors' conclusion
KEAP1 germline heterozygous mutations exert excessive NRF2 activity in the thyroid gland and may confer cytoprotective effects even under abundant reactive oxygen species associated with thyroid hormone production, resulting in thyroid hyperplasia with scarce degradation.
Study context
- Population
- Patients with familial multinodular goiter; KEAP1 germline mutation carriersfamilial multinodular goiter
- Participants
- 39 patients
- Outcome
- KEAP1 mutations and nodular NRF2-targeted gene expression
Methodological detailsnext-generation sequencing, whole-transcript expression array, immunohistochemistry
- Next-generation sequencing
- Whole-transcript expression array
- Immunohistochemistry
Main finding
As reported in the abstract
Probands with pathogenic heterozygous KEAP1 mutations (p.Q86*, p.L136P, p.V411fs, p.R415C, p.R483H); no meaningful concomitance with mutations of other goiter-associated genes
5
Histopathology: multinodular goiters in the entire thyroid with few degenerative lesions or complications of malignancy; Ki-67 labeling index
less than 1%
Antioxidant genes upregulated in the nodule (most frequent, among 42 NRF2-targeted genes)
11 of 12
Detoxification genes upregulated in the nodule
6 of 11
Original publication
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