Two G protein oncogenes in human endocrine tumors.
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.
Lyons
J
J
Department of Human Genetics, Cetus Corporation, Emeryville CA 94608.
Landis
C A
CA
Harsh
G
G
Vallar
L
L
Grünewald
K
K
Feichtinger
H
H
Duh
Q Y
QY
Clark
O H
OH
Kawasaki
E
E
Bourne
H R
HR
D000595:Amino Acid Sequence; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics; D004700:Endocrine System Diseases / Q000235:genetics*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D015345:Oligonucleotide Probes; D009857:Oncogenes; D010911:Pituitary Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D015345:Oligonucleotide Probes; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins