Ras mutations in human pituitary tumors.
The cellular basis for pituitary neoplasia is poorly understood. Mutations that activate the ras protooncogenes have been identified in a number of different types of human cancers and potentially represent one of the genetic alterations that occur in pituitary tumors. In this study we examined 19 pituitary tumors for the occurrence of ras mutations. The tumor types included 11 nonfunctioning adenomas, 6 somatotroph adenomas, and 2 prolactinomas. Each of the three ras genes (K-ras, N-ras, and H-ras) was amplified from pituitary tumor DNA using the polymerase chain reaction. Oligonucleotide-specific hybridization was used to screen for mutations that inhibit GTPase activity and cause activation of the ras oncogene. No ras mutations were observed in 18 of the pituitary adenomas. However, a mutation was identified in codon 12 of the H-ras gene (Gly to Val) in a recurrent prolactinoma that was highly invasive and ultimately proved to be fatal. We conclude that ras mutations are uncommon in pituitary adenomas, but may provide a marker for highly invasive tumors.
Karga
H J
HJ
Department of Medicine, Massachusetts General General Hospital, Boston 02114.
Alexander
J M
JM
Hedley-Whyte
E T
ET
Klibanski
A
A
Jameson
J L
JL
D000236:Adenoma / Q000737:chemistry / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D015689:Oncogene Protein p21(ras) / Q000032:analysis / Q000235:genetics; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011388:Prolactin / Q000032:analysis; D015175:Prolactinoma / Q000737:chemistry / Q000235:genetics*; D011863:Radioimmunoassay
D004273:DNA, Neoplasm; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015689:Oncogene Protein p21(ras)