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Science 10 August 1990:
Vol. 249. no. 4969, pp. 655 - 659
DOI: 10.1126/science.2116665
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Articles

Science, Vol 249, Issue 4969, 655-659
Copyright © 1990 by American Association for the Advancement of Science

articles

Two G protein oncogenes in human endocrine tumors

J Lyons, CA Landis, G Harsh, L Vallar, K Grunewald, H Feichtinger, QY Duh, OH Clark, E Kawasaki, HR Bourne, and al. et

Department of Human Genetics, Cetus Corporation, Emeryville CA 94608.

Somatic mutations in a subset of growth hormone (GH)-secreting pituitary tumors convert the gene for the alpha polypeptide chain (alpha s) of Gs into a putative oncogene, termed gsp. These mutations, which activate alpha s by inhibiting its guanosine triphosphatase (GTPase) activity, are found in codons for either of two amino acids, each of which is completely conserved in all known G protein alpha chains. The likelihood that similar mutations would activate other G proteins prompted a survey of human tumors for mutations that replace either of these two amino acids in other G protein alpha chain genes. The first gene so far tested, which encodes the alpha chain of Gi2, showed mutations that replaced arginine-179 with either cysteine or histidine in 3 of 11 tumors of the adrenal cortex and 3 of 10 endocrine tumors of the ovary. The mutant alpha i2 gene is a putative oncogene, referred to as gip2. In addition, gsp mutations were found in 18 of 42 GH-secreting pituitary tumors and in an autonomously functioning thyroid adenoma. These findings suggest that human tumors may harbor oncogenic mutations in various G protein alpha chain genes.


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Clonal Origin of Toxic Thyroid Nodules with Constitutively Activating Thyrotropin Receptor Mutations.
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No Evidence of a Role for Mutations or Polymorphisms of the Follicle-Stimulating Hormone Receptor in Ovarian Granulosa Cell Tumors.
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Crystal Structure of the Adenylyl Cyclase Activator Gsalpha .
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The Thyrotropin Receptor in Thyroid Diseases.
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A Novel Transcript for the Thyrotropin-Releasing Hormone Receptor in Human Pituitary and Pituitary Tumors.
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