H-ras oncogene activation in invasive UVR-induced corneal sarcomas of the opossum Monodelphis domestica.
Chronic exposure to ultraviolet radiation (UVR) induces corneal sarcomas in the South American opossum Monodelphis domestica. Cell lines are readily established from these tumors. Northern blotting of mRNA from six such cell lines revealed high expression of the H-ras oncogene. H-ras cDNA from an eye tumor cell line was cloned and characterized; the germline sequence of codons 12, 13, and 61 was confirmed by examination of H-ras sequences amplified from liver DNA by the polymerase chain reaction. The Monodelphis H-ras coding sequence is 84-89% identical to that of other vertebrates at the nucleotide level, and the predicted 189-amino-acid sequence differs by 2-12 amino acids from that of other vertebrates. Analysis of 12 primary invasive corneal sarcomas induced by chronic UVR exposure revealed no evidence of H-ras gene amplification or rearrangement. One tumor was heterozygous for an activating point mutation in codon 61 of the H-ras gene; the tumor was also homozygous for a point mutation at an adjacent site in codon 62. These results provide additional evidence for the functional importance and consequent evolutionary conservation of the ras oncogenes.
Kusewitt
D F
DF
Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
Gale
J M
JM
Sherburn
T E
TE
Tafoya
G B
GB
Ley
R D
RD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D003316:Corneal Diseases / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005134:Eye Neoplasms / Q000235:genetics*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D008969:Molecular Sequence Data; D009893:Opossums; D017354:Point Mutation / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012513:Sarcoma, Experimental / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014466:Ultraviolet Rays
D003062:Codon; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm