PMID- 10037070
OWN - NLM
STAT- MEDLINE
DCOM- 19990602
LR  - 20161124
IS  - 1050-7256 (Print)
IS  - 1050-7256 (Linking)
VI  - 9
IP  - 1
DP  - 1999 Jan
TI  - A Val 677 activating mutation of the thyrotropin receptor in a Hurthle cell
      thyroid carcinoma associated with thyrotoxicosis.
PG  - 13-7
AB  - Thyroid nodules presenting as hot at 131I-scintigraphy are usually benign
      follicular adenomas. We report a 42-year-old female patient with an autonomously 
      functioning Hurthle cell thyroid carcinoma causing thyrotoxicosis. Genetic
      analysis of her thyroid tumoral DNA revealed a heterozygotic activating mutation 
      of the thyrotropin receptor (TSHR) gene that was located downstream to all of the
      other genetic alterations currently identified, and is due to a base substitution
      at codon 677 (normal cytosine replaced by guanine, CTG for GTG causing leucine
      substitution by valine in the seventh transmembrane domain of the receptor). This
      mutation was detected in the tumor, but not in the leucocytes from the same
      patient. The Val 677-TSHR mutant showed constitutive activity, in terms of cyclic
      adenosine monophosphate (cAMP) production, when permanently transfected in
      Chinese hamster ovary (CHO) cells. Gsp and ras oncogenes and the p53 tumor
      suppressor gene were not present in the Hurthle cell cancer. The TSHR mutation in
      this Hurthle cell carcinoma may be responsible for maintaining differentiated
      thyroid function and hyperthyroidism.
FAU - Russo, D
AU  - Russo D
AD  - Dipartimento di Medicina Sperimentale e Clinica, Cattedra di Endocrinologia,
      University of Catanzaro, Italy.
FAU - Wong, M G
AU  - Wong MG
FAU - Costante, G
AU  - Costante G
FAU - Chiefari, E
AU  - Chiefari E
FAU - Treseler, P A
AU  - Treseler PA
FAU - Arturi, F
AU  - Arturi F
FAU - Filetti, S
AU  - Filetti S
FAU - Clark, O H
AU  - Clark OH
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (DNA, Complementary)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Receptors, Thyrotropin)
RN  - 1F7A44V6OU (Colforsin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Adenocarcinoma/diagnostic imaging/*genetics/pathology/surgery
MH  - Adult
MH  - Animals
MH  - CHO Cells
MH  - Colforsin/pharmacology
MH  - Cricetinae
MH  - Cyclic AMP/metabolism
MH  - DNA Mutational Analysis
MH  - DNA, Complementary/genetics
MH  - Female
MH  - Heterozygote
MH  - Humans
MH  - Iodine Radioisotopes
MH  - Point Mutation
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Radionuclide Imaging
MH  - Receptors, Thyrotropin/*genetics
MH  - Thyroid Gland/diagnostic imaging/*pathology/surgery
MH  - Thyroid Neoplasms/diagnostic imaging/*genetics/pathology/surgery
MH  - Thyroidectomy
MH  - Thyrotoxicosis/*etiology
MH  - Transfection
MH  - Valine/*genetics
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
AID - 10.1089/thy.1999.9.13 [doi]
PST - ppublish
SO  - Thyroid. 1999 Jan;9(1):13-7. doi: 10.1089/thy.1999.9.13.