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Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas.
Sci Rep. 2017 04 21; 7(1):1015.SR

Abstract

Up to 86% of uterine leiomyomas harbour somatic mutations in mediator complex subunit 12 (MED12). These mutations have been associated with conventional histology, smaller tumour size, and larger number of tumours within the uterus. Prior studies, with limited sample sizes, have failed to detect associations between other clinical features and MED12 mutations. Here, we prospectively collected 763 uterine leiomyomas and the corresponding normal myometrial tissue from 244 hysterectomy patients, recorded tumour characteristics, collected clinical data from medical records, and screened the tissue samples for MED12 mutations to assess potential associations between clinical variables and mutation status. Out of 763 leiomyomas, 599 (79%) harboured a MED12 mutation. In the analysis of tumour characteristics, positive MED12-mutation status was significantly associated with smaller tumour size, conventional histology, and subserous location, relative to intramural. In the analysis of clinical variables, the number of MED12-mutation-positive tumours showed an inverse association with parity, and the number of mutation-negative tumours showed a positive association with a history of pelvic inflammatory disease. This study confirmed the previously reported differences and discovered novel differentiating features for MED12-mutation-positive and -negative leiomyomas. These findings emphasise the relevance of specific driver mutations in genesis and presentation of uterine leiomyomas.

Authors+Show Affiliations

Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.Department of Pathology, P.O. Box 21, FIN-00014 University of Helsinki and Helsinki University Hospital, Helsinki, Finland.Department of Obstetrics and Gynaecology, P.O. Box 140, FIN-00029 University of Helsinki and Helsinki University Hospital, Helsinki, Finland.Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.Department of Obstetrics and Gynaecology, P.O. Box 140, FIN-00029 University of Helsinki and Helsinki University Hospital, Helsinki, Finland.Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.Department of Pathology, P.O. Box 21, FIN-00014 University of Helsinki and Helsinki University Hospital, Helsinki, Finland.Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland. lauri.aaltonen@helsinki.fi.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28432313

Citation

Heinonen, Hanna-Riikka, et al. "Multiple Clinical Characteristics Separate MED12-mutation-positive and -negative Uterine Leiomyomas." Scientific Reports, vol. 7, no. 1, 2017, p. 1015.
Heinonen HR, Pasanen A, Heikinheimo O, et al. Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas. Sci Rep. 2017;7(1):1015.
Heinonen, H. R., Pasanen, A., Heikinheimo, O., Tanskanen, T., Palin, K., Tolvanen, J., Vahteristo, P., Sjöberg, J., Pitkänen, E., Bützow, R., Mäkinen, N., & Aaltonen, L. A. (2017). Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas. Scientific Reports, 7(1), 1015. https://doi.org/10.1038/s41598-017-01199-0
Heinonen HR, et al. Multiple Clinical Characteristics Separate MED12-mutation-positive and -negative Uterine Leiomyomas. Sci Rep. 2017 04 21;7(1):1015. PubMed PMID: 28432313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas. AU - Heinonen,Hanna-Riikka, AU - Pasanen,Annukka, AU - Heikinheimo,Oskari, AU - Tanskanen,Tomas, AU - Palin,Kimmo, AU - Tolvanen,Jaana, AU - Vahteristo,Pia, AU - Sjöberg,Jari, AU - Pitkänen,Esa, AU - Bützow,Ralf, AU - Mäkinen,Netta, AU - Aaltonen,Lauri A, Y1 - 2017/04/21/ PY - 2017/02/03/received PY - 2017/03/27/accepted PY - 2017/4/23/entrez PY - 2017/4/23/pubmed PY - 2018/9/19/medline SP - 1015 EP - 1015 JF - Scientific reports JO - Sci Rep VL - 7 IS - 1 N2 - Up to 86% of uterine leiomyomas harbour somatic mutations in mediator complex subunit 12 (MED12). These mutations have been associated with conventional histology, smaller tumour size, and larger number of tumours within the uterus. Prior studies, with limited sample sizes, have failed to detect associations between other clinical features and MED12 mutations. Here, we prospectively collected 763 uterine leiomyomas and the corresponding normal myometrial tissue from 244 hysterectomy patients, recorded tumour characteristics, collected clinical data from medical records, and screened the tissue samples for MED12 mutations to assess potential associations between clinical variables and mutation status. Out of 763 leiomyomas, 599 (79%) harboured a MED12 mutation. In the analysis of tumour characteristics, positive MED12-mutation status was significantly associated with smaller tumour size, conventional histology, and subserous location, relative to intramural. In the analysis of clinical variables, the number of MED12-mutation-positive tumours showed an inverse association with parity, and the number of mutation-negative tumours showed a positive association with a history of pelvic inflammatory disease. This study confirmed the previously reported differences and discovered novel differentiating features for MED12-mutation-positive and -negative leiomyomas. These findings emphasise the relevance of specific driver mutations in genesis and presentation of uterine leiomyomas. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/28432313/Multiple_clinical_characteristics_separate_MED12_mutation_positive_and__negative_uterine_leiomyomas_ L2 - http://dx.doi.org/10.1038/s41598-017-01199-0 DB - PRIME DP - Unbound Medicine ER -