Loss of IGF-II imprinting in endometrial tumors: overexpression in carcinosarcoma.
The genomic imprinting of the maternal allele defines the monoallelic expression of the IGF-II gene in most human tissues. The loss of imprinting (LOI) leading to biallelic overexpression of IGF-II has been reported in several human malignancies, including uterine leiomyosarcoma. To ascertain if LOI occurs in endometrial malignancies, the allelic expression of the IGF-II gene was examined in samples of normal human endometrium (n=22) and endometrial tumors (n=12) by assessing the ApaI polymorphism in cDNA segments amplified by RT-PCR. The biallelic overexpression of IGF-II mRNA, involving activation of all four (P1-P4) promoters, was detected in one normal endometrium and in one endometrial carcinosarcoma. Low level biallelic expression of IGF-II was also detected in two samples of hormone-unresponsive/Type II endometrial carcinomas. The level of IGF-I mRNA in these four samples was low. The IGF-IR mRNA was overexpressed in all endometrial cancers including the carcinosarcoma sample, but not in normal endometrium. These data suggest that LOI associated with overexpression of IGF-II and concomitant overexpression of IGF-IR may play a role in the rare carcinosarcoma of the endometrium.
Roy
R N
RN
Department of Obstetrics and Gynecology, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.
Gerulath
A H
AH
Cecutti
A
A
Bhavnani
B R
BR
D002296:Carcinosarcoma / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1