Korean J Gynecol Oncol Colposc.  1994 Jun;5(2):10-23.

Detection of c-K-ras Oncogene Point Mutations in Cancers of the Female Genital Tract

• Koh YM
• Kim HK
• Park JS
• Han SK
• Kim W
• Lee PH
• Namkoong S
• Kim SJ

Abstract

It hae been well established that, specifi alterations in members of the ras gene family, H-ras, K-ras and N-ras, can convert them into active oncogenes. These alterations are either point mutations occurirg in either codon 12, 13 or 61, or alternatively, a 5- to 50-fold amplification of the wfld-type gene. Activated ras oncogenes have been found in a significant proportion of all turnors, but the incidence varies considerably with the tumor type : it is frequent (20~40%) in colarectal eancer and acute myeloid leukemia, but absent or preaent rarely in breast and atomach cancer. But the role of c-K-ras point mutatio in the development of cancers in the female genital tract has not been extensively studied. Polymerase chain reaction followed by gel electrophoresis was performed respectively using wild-type normal and specific point mutation primers{GGT->GAT, GGT->AGT, GGT->TGT and GGT->GTT) to detect, point, mutation of codon 12 of c-K-ras oncogene. The c-K-ras oncogene point mutation was confirmed by Southern blot hybridization using synthetic oligonucleatide probe. 3'-end Iabelled with digoxigenin -dUTP. With this method, the frequency of point mutation on codon 12 of c-K-ras oncogene was examined the tissues in 37 casea of ovarian cancer, 7 cases of endometrial cancer, 36 cases of the gestational trophoblastic tumor, 60 cases of cervical cancer. The relationship between the presence of a c-K-ras point mutation and clinicopathological characteristics of the female genital tract cancers were also analysed. The results were as follows; 1. The incidence of four point mutations on codon 12 of c-K-ras oncogene in 37 ovarian cancers was 45.9% (17/37) and distribution were 43.2% (16/37), 2.7% (1/37) and 0% (0/37) in GGT-->GAT, GGT-->AGT, GGT-->TGT, and GGT-->GTT, respectively. According to histological type, in ovarian cancers, The point mutation of K-ras oncogene waspositive in 45 % (10/22) of serous cystadenocarcinomas. The incidence of four point mutations on codon 12 among 37 patients with ovarian cancer according to histological type was 45.5 % (10/22) with serous cystadenocarcinoma, 57.1% (4/7) of mucinous cystadenocarcinoma. Comparing the positive rate of point mutations of K-ras oncogen among 37 patients with ovarian cancer with the clinical stage, point mutation was detected in 28.5% (2/7) of patients with stage I, 40.0% (2/5) with stage II, and 52.0% (13/25) with stage III/IV. There was no statistically significant increasement of point mutations with the advance of the clinical stage of ovarian cancer. Comparing the positive rate of point mutations of K-ras oncogen among 37 patients with ovarian cancer according to the histologic grade point mutation was detected in 50.0 % (2/4) 0f patients with grade I, 451.7 % (5/12) with grade II and 47.6 % (10/21) with grade III. 2. The incidence of point mutations of K-ras oncogen among 33 patients with ovarian cancer who were performed pelvic lymph node dissection was 57.1 % (12/21) of the patients with pelvic lymph node metastases and 16.7% (2/12) of the patients without pelvic lymph node metastases. There was statistically significant difference between the positive rate of c-K-ras point mutations and the pelvic lymph nodal status(P<0.05). 3. In 7 cases of endometrial cancer, positive rate of K-ras point was 42.8 % (3/7). Point mutations were also detected in 2 cases from 4 choriocarcinomas, but, the point mutation was only detected in 1 case from 60 cervical carcinomas. From these results, we may suggest that the point mutation on codon 12 c-K-ras oncogene are considered to be one of the important genetic change in the tumor formation and progression of ovarian of c-K-ras oncogene seems to be the one stop in the multistep process of tumor formation in ovarian cancer. Furthermore, the point mutation of c-k-ras gene could occur more frequently in the patients of ovarian cancer with pelvic lymph node metastases than in those without pelvic metastases, suggesting the orle in tumor progression. And we concluded that point mutation on codon 12 is comparable frequent in uterine endometrial carcinomas and have significance as an event that contributes to progrssion of endometrial cancers and choriocarcinoma, but cervical carcinoma do not appear to have c-K-ras point mutation in general. More studies will be necessary, but the detection of c-k-ras point mutation as the possibility of biological tumor marker to predict clinical outcome may be utilized in female malignancies.

MeSH Terms

Blotting, Southern
Breast
Choriocarcinoma
Codon
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Digoxigenin
Electrophoresis
Endometrial Neoplasms
Female*
Genes, ras
Humans
Incidence
Leukemia, Myeloid, Acute
Lymph Node Excision
Lymph Nodes
Neoplasm Metastasis
Oncogenes*
Ovarian Neoplasms
Point Mutation*
Polymerase Chain Reaction
Pregnancy
Trophoblastic Neoplasms
Biomarkers, Tumor
Uterine Cervical Neoplasms
Codon
Digoxigenin