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HMGA2 and MED12 alterations frequently co-occur in uterine leiomyomas.
- Source :
-
Gynecologic oncology [Gynecol Oncol] 2018 Sep; Vol. 150 (3), pp. 562-568. Date of Electronic Publication: 2018 Jul 13. - Publication Year :
- 2018
-
Abstract
- Objective: Around 70% of uterine leiomyomas show MED12 mutations while overexpression of HMGA2 mRNA is also highly frequent in fibroids. However, previous studies suggested that alterations in both genes are mutually exclusive. In the present study, we searched for mutation in MED12 and analyzed the expression of HMGA2 in 20 uterine leiomyomas and their matched myometrium.<br />Methods: Normal and tumor tissue obtained from premenopausal women who underwent hysterectomy were collected after surgery and DNA, RNA and proteins were isolated and analyzed for MED12 mutations using Sanger sequencing, HMGA2 mRNA expression by quantitative PCR and HMGA2 protein detection by western blot and immunohistochemistry.<br />Results: 75% of the tumors displayed MED12 mutation while 65% of them showed overexpression of HMGA2 mRNA in leiomyomata compared to myometrial tissues (p = 0,0008). Interestingly, 50% of the tumors showed mutations in MED12 and overexpression of HMGA2 mRNA simultaneously, suggesting that alterations in both genes are relatively frequent in uterine leiomyomas.<br />Conclusions: Contrary to the present findings, former studies showed that mutations in MED12 and overexpression of HMGA2 are mutually exclusive. Here, we observed that overexpression of HMGA2 mRNA in tumors measured by quantitative PCR and compared to myometrium is a common phenomenon in fibroids and is frequently associated with MED12 mutations. In addition, the common clonal origin of tumors overexpressing HMGA2 mRNA and its expression in few myometrial tissue points to HMGA2 up-regulation as an early event in leiomyoma tumorigenesis.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Female
Gene Expression
HMGA2 Protein metabolism
Humans
Leiomyoma metabolism
Mediator Complex metabolism
Middle Aged
Mutation
Myometrium metabolism
Premenopause
Uterine Neoplasms metabolism
HMGA2 Protein genetics
Leiomyoma genetics
Mediator Complex genetics
RNA, Messenger metabolism
Uterine Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6859
- Volume :
- 150
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Gynecologic oncology
- Publication Type :
- Academic Journal
- Accession number :
- 30017537
- Full Text :
- https://doi.org/10.1016/j.ygyno.2018.07.007