title: K-ras activation occurs frequently in mucinous adenocarcinomas and rarely in other common epithelial tumors of the human ovary.
abstract: To explore the role of mutational activation of members of the ras family of cellular protooncogenes in the development of human ovarian neoplasms, a series of 37 ovarian tumors from Japanese patients was studied. These included 30 common epithelial tumors (1 mucinous tumor of borderline malignancy, 7 mucinous adenocarcinomas, and 22 nonmucinous carcinomas: 10 serous, 3 clear cell, 8 endometrioid, and 1 undifferentiated), 5 tumors of germ cell origin, and 2 sex cord/stromal cell tumors. Polymerase chain reaction was performed from selected areas of deparaffinized sections of formalin-fixed paraffin-embedded tissue, and the presence of activating point mutations in codons 12, 13, and 61 of the H-, N-, and K-ras genes was probed by dot-blot hybridization analysis with mutation specific oligonucleotides. Mutations in K-ras were also looked for by direct genomic sequencing. The overall frequency of ras gene mutations was 10/37 (27%). Mutations were detected only in K-ras, and were found in most of the mucinous tumors, including the one such tumor of borderline malignancy (6/8; 75%). In one mucinous adenocarcinoma, two mutations were detected in paraffin-embedded material that had not previously been found in high molecular weight DNA isolated from frozen tissue from the same case. K-ras mutations occurred significantly more frequently in mucinous tumors (6/8, 75%) than in serous carcinomas (2/10, 20%; P = 0.031) or in all nonmucinous types of epithelial ovarian tumors combined (3/22, 14%; P = 0.0031).
authors.affiliation: Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland.
authors.forename: T
authors.initials: T
authors.lastname: Enomoto
authors.forename: C M
authors.initials: CM
authors.lastname: Weghorst
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: O
authors.initials: O
authors.lastname: Tanizawa
authors.forename: J M
authors.initials: JM
authors.lastname: Rice
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm