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MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma.
Mod Pathol. 2014 Aug; 27(8):1144-53.MP

Abstract

Recent identification of somatic MED12 mutations in most uterine leiomyomas brings a new venue for the study of the tumorigenesis of leiomyomas. We are particularly interested in the correlation of MED12 and HMGA2 gene products in leiomyomas and leiomyosarcomas with and without MED12 mutations. To address these issues, in this study we examined MED12 mutations in a large cohort of usual type leiomyomas (178 cases) and uterine leiomyosarcomas (32 cases). We found that 74.7% (133/178) of leiomyomas had MED12 mutations, which was consistent with several independent studies. In contrast, only 9.7% (3/32) of leiomyosarcomas harbored MED12 mutations. Expression analysis by western blot and immunohistochemistry revealed that those leiomyomas with complex MED12 mutations had significantly lower protein products than the matched myometrium. Interestingly, most leiomyosarcomas without MED12 mutations also had very low levels of MED12 expression in comparison to the matched myometrium. These findings suggest a potential functional role of MED12 in both benign and malignant uterine smooth muscle tumors. When we further examined HMGA2 expression in all leiomyomas and leiomyosarcomas, we found that HMGA2 overexpression was exclusively present in those leiomyomas with no MED12 mutation, accounting for 10.1% (18/178) of total leiomyomas and 40% (18/45) of non-MED12 mutant leiomyomas. Twenty-five percent (8/32) of leiomyosarcomas had HMGA2 overexpression, and no MED12 mutations were found in HMGA2 positive leiomyosarcoma. These findings strongly suggest that MED12 mutations and HMGA2 overexpression are independent genetic events that occur in leiomyomas, and they may act differently in the tumorigenesis of uterine leiomyomas.

Authors+Show Affiliations

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.Department of Gynecology and Obstetrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.1] Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA [2] Department of Gynecology and Obstetrics, Shandong University, Jinan, China.Department of Gynecology and Obstetrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.Department of Gynecology and Obstetrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.Department of Gynecology and Obstetrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.Department of Pathology, Longue Medical School, New York University, New York, NY, USA.Department of Gynecology and Obstetrics, Shandong University, Jinan, China.Department of Gynecology and Obstetrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.1] Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA [2] Department of Gynecology and Obstetrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24390224

Citation

Bertsch, Elizabeth, et al. "MED12 and HMGA2 Mutations: Two Independent Genetic Events in Uterine Leiomyoma and Leiomyosarcoma." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 27, no. 8, 2014, pp. 1144-53.
Bertsch E, Qiang W, Zhang Q, et al. MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. Mod Pathol. 2014;27(8):1144-53.
Bertsch, E., Qiang, W., Zhang, Q., Espona-Fiedler, M., Druschitz, S., Liu, Y., Mittal, K., Kong, B., Kurita, T., & Wei, J. J. (2014). MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 27(8), 1144-53. https://doi.org/10.1038/modpathol.2013.243
Bertsch E, et al. MED12 and HMGA2 Mutations: Two Independent Genetic Events in Uterine Leiomyoma and Leiomyosarcoma. Mod Pathol. 2014;27(8):1144-53. PubMed PMID: 24390224.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. AU - Bertsch,Elizabeth, AU - Qiang,Wenan, AU - Zhang,Qing, AU - Espona-Fiedler,Margarita, AU - Druschitz,Stacy, AU - Liu,Yu, AU - Mittal,Khush, AU - Kong,Beihua, AU - Kurita,Takeshi, AU - Wei,Jian-Jun, Y1 - 2014/01/03/ PY - 2013/09/04/received PY - 2013/11/14/revised PY - 2014/11/26/accepted PY - 2014/1/7/entrez PY - 2014/1/7/pubmed PY - 2015/4/14/medline SP - 1144 EP - 53 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod. Pathol. VL - 27 IS - 8 N2 - Recent identification of somatic MED12 mutations in most uterine leiomyomas brings a new venue for the study of the tumorigenesis of leiomyomas. We are particularly interested in the correlation of MED12 and HMGA2 gene products in leiomyomas and leiomyosarcomas with and without MED12 mutations. To address these issues, in this study we examined MED12 mutations in a large cohort of usual type leiomyomas (178 cases) and uterine leiomyosarcomas (32 cases). We found that 74.7% (133/178) of leiomyomas had MED12 mutations, which was consistent with several independent studies. In contrast, only 9.7% (3/32) of leiomyosarcomas harbored MED12 mutations. Expression analysis by western blot and immunohistochemistry revealed that those leiomyomas with complex MED12 mutations had significantly lower protein products than the matched myometrium. Interestingly, most leiomyosarcomas without MED12 mutations also had very low levels of MED12 expression in comparison to the matched myometrium. These findings suggest a potential functional role of MED12 in both benign and malignant uterine smooth muscle tumors. When we further examined HMGA2 expression in all leiomyomas and leiomyosarcomas, we found that HMGA2 overexpression was exclusively present in those leiomyomas with no MED12 mutation, accounting for 10.1% (18/178) of total leiomyomas and 40% (18/45) of non-MED12 mutant leiomyomas. Twenty-five percent (8/32) of leiomyosarcomas had HMGA2 overexpression, and no MED12 mutations were found in HMGA2 positive leiomyosarcoma. These findings strongly suggest that MED12 mutations and HMGA2 overexpression are independent genetic events that occur in leiomyomas, and they may act differently in the tumorigenesis of uterine leiomyomas. SN - 1530-0285 UR - https://www.unboundmedicine.com/medline/citation/24390224/MED12_and_HMGA2_mutations:_two_independent_genetic_events_in_uterine_leiomyoma_and_leiomyosarcoma_ L2 - http://dx.doi.org/10.1038/modpathol.2013.243 DB - PRIME DP - Unbound Medicine ER -