Early mutational activation of the c-Ki-ras oncogene in endometrial carcinoma.
Endometrial carcinoma is theorized to arise from a series of somatic mutations which alter benign endometrium to progressively less differentiated histological lesions. One genetic alteration implicated in the carcinogenesis of endometrial cancer is the mutational activation of the c-Ki-ras oncogene. This study characterizes the frequency and the topographical distribution of activated c-Ki-ras alleles in endometrial carcinoma. Sixty formalin-fixed, paraffin-embedded endometrial cancer specimens were screened for point mutations at codons 12 and 13 of the c-Ki-ras oncogene by polymerase chain reaction and allelic specific oligomer dot-blot hybridization. c-Ki-ras mutations were identified in nine of 60 (15%) tumor specimens. Five cases resulted in G to A transitions, three in G to T transversions, and one in a G to C transversion. These nine mutant tumors were analyzed by selective UV radiation fractionation and polymerase chain reaction for the presence of activated c-Ki-ras alleles in cell populations of various histological phenotype. In eight tumors, c-Ki-ras mutations were uniformly present in the carcinoma cells. One tumor exhibited heterogeneous mutational activation, with mutant c-Ki-ras alleles detected in only grade 2 carcinoma cells but not grade 1 carcinoma cells. c-Ki-ras mutations were present in adjacent hyperplasia with atypia but absent from hyperplasia without atypia. With rare exception, c-Ki-ras activation appears to be an early oncogenic event since it is homogeneously present in premalignant and malignant endometrial tissues.
Duggan
B D
BD
Department of Obstetrics and Gynecology, Los Angeles County-University of Southern California Medical Center 90033.
Felix
J C
JC
Muderspach
L I
LI
Tsao
J L
JL
Shibata
D K
DK
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*