Details Of Published TSH Receptor Mutation
Met 453 Thr
c.1358T>CConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
carcinoma
Exon
10
Molecular Characteristics:
papillary thyroid carcinoma
Clinical Features:
*based on 3 hot thyroid carcinoma investigated by Mircescu et al. 2000, Lado-Abeal et al. 2010, Xu et al. 2019
Lado-Abeal: co-occuring with Pax8PPAR?
Xu: Also had the following copy number alterations: Gain of 5, 10, 12, 17, 18, 20, 21, X; WCD of 7; Copy neutral LOH in 9
Lado-Abeal: co-occuring with Pax8PPAR?
Xu: Also had the following copy number alterations: Gain of 5, 10, 12, 17, 18, 20, 21, X; WCD of 7; Copy neutral LOH in 9
Treatment:
Lado-Abeal: total thyroidectomy, 2 years L-T4 suppressive
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.7-7.0
0.8
1.0
0.8-1.0
nd
0.66
3
5.2+/-0.8
1,3,4
Legend:
cAMP (basal): basal in vitro cAMP production of mutant over wild-type TSHR
cAMP (TSH): maximal in vitro cAMP production of mutant over wild-type TSHR
IP (basal): basal in vitro IP production of mutant over wild-type TSHR
IP (TSH): maximal in vitro IP production of mutant over wild-type TSHR
TSH-binding: maximal TSH-binding compared to the wild-type TSHR
Cell surface expression: cell surface expression of mutant compared to WT-TSHR
LRA: linear regression analysis (LRA) of constitutive activity as a function of TSHR expression determined by 125I-bTSH binding or FACS analysis compared to the wild-type TSHR
Prevalence: Prevalence of (somatic and germline) activating mutations*
Ref: Reference for functional characterization
Child: Found in children.
Reference 1:
De Roux et al.
J. Clin. Endocrinol. Metab. 81: 2023-2026
A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism.
1996
Reference 2:
Mircescu et al.
J. Paediatr. 137: 585-587
Hyperfunctioning malignant thyroid nodule in an 11-year-old girl: pathologic and molecular studies.
2000
Reference 3:
Jäschke et al.
Cell Mol Life Sci 65:4028-4038
Preferences of transmembrane helices for cooperative amplification of G(alpha)s and G (alpha)q signaling of the thyrotropin receptor.
2008
Reference 4:
Lüblinghoff et al.
J Endocrinol Invest 33:228-233
Lack of consistent association of thyrotropin receptor mutations in vitro activity with the clinical course of patients with sporadic non-autoimmune hyperthyroidism.
2010
Reference 5:
Xu et al.
Endocrine-related cancer
Outcome and molecular characteristics of non-invasive encapsulated follicular variant of papillary thyroid carcinoma with oncocytic features
2019