Screening of Candidate Oncogenes in Human Thyrotroph Tumors: Absence of Activating Mutations of the Gαq, Gα11, Gαs, or Thyrotropin-Releasing Hormone Receptor Genes

Qihan Dong, Françoise Brucker-Davis, Bruce D. Weintraub, Robert C. Smallridge, Frances E. Carr, James Battey, Allen M. Spiegel, Andrew Shenker

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Activating mutations encoding substitutions at positions Arg201 and Gln227 of the α-subunit of the stimulatory G protein, Gs, have been found in about 40% of pituitary somatotroph tumors. Although the etiology of thyrotroph adenomas is unknown, their autonomous behavior and blunted response to stimulatory hypothalamic hormone superficially resemble those of somatotroph tumors. We hypothesized that a subset of thyrotroph tumors might be caused by dominant somatic mutations that lead to inappropriate activation of the Gq/ phospholipase Cβ/Ca2+/protein kinase C pathway normally triggered by occupancy of the TRH receptor (TRHR). We, therefore, screened samples from nine thyrotroph tumors for the presence of activating mutations of the αq, α11, and TRHR genes. Fragments of αq and α11 complementary DNA encompassing residues (Arg183 and Gln209) that correspond to Arg201 and Gln227 of αs were amplified and sequenced. Temperature gradient gel electrophoresis was used to screen for heterozygous mutations in the TRHR coding sequence as well as for known αs mutations. No mutations were detected. We conclude that mutations in these regions of the αq, α11, αs, and TRHR genes occur infrequently, if at all, in human thyrotroph tumors. Alternative mechanisms underlying thyrotroph tumorigenesis, including changes in the expression levels of G protein α-subunits or TRHR, dysregulation of downstream components, inappropriate activation of other stimulatory pathways, or loss of inhibitory inputs, remain to be explored.

Original languageEnglish (US)
Pages (from-to)1134-1140
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number3
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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