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MED12 exon 2 mutations in histopathological uterine leiomyoma variants.
Eur J Hum Genet. 2013 Nov; 21(11):1300-3.EJ

Abstract

Uterine leiomyomas, or fibroids, are the most common human tumors. Based on histopathology, they can be divided into common leiomyomas and various relatively rare subtypes that mimic malignancy in one or more aspects. Recently, we showed that exon 2 of mediator complex subunit 12 (MED12) is mutated in up to 70% of common fibroids. To investigate the frequency of MED12 exon 2 mutations in histopathological uterine leiomyoma variants, we screened altogether 206 lesions, including 69 histopathologically common leiomyomas, 59 cellular (23 cellular and 36 highly cellular), 18 atypical and 26 mitotically active leiomyomas, as well as 34 uterine fibroid samples from 14 hereditary leiomyomatosis and renal cell cancer patients with a heterozygous germ line mutation in fumarate hydratase (FH). The uterine leiomyoma variants harbored MED12 exon 2 mutations significantly less frequently than common leiomyomas (P=2.93 × 10(-8)). In all, 6 mutations were detected among cellular fibroids (6/67; 8.96%), 3 among atypical fibroids (3/18; 16.67%) and 10 among mitotically active fibroids (10/26; 38.46%). Only mitotically active fibroids displayed a mutation frequency that was not statistically different from common leiomyomas (P=0.11). Three MED12 exon 2 mutations were detected among 34 tumors with a heterozygous germ line FH mutation (P=5.28 × 10(-7)). None of these tumors displayed biallelic inactivation of FH. Our results suggest that MED12 mutation positivity is a key characteristic of common leiomyomas. Cellular and atypical fibroids, in particular, may arise through different molecular mechanisms. The results also propose that MED12 and biallelic FH mutations may be mutually exclusive.

Authors+Show Affiliations

Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23443020

Citation

Mäkinen, Netta, et al. "MED12 Exon 2 Mutations in Histopathological Uterine Leiomyoma Variants." European Journal of Human Genetics : EJHG, vol. 21, no. 11, 2013, pp. 1300-3.
Mäkinen N, Vahteristo P, Kämpjärvi K, et al. MED12 exon 2 mutations in histopathological uterine leiomyoma variants. Eur J Hum Genet. 2013;21(11):1300-3.
Mäkinen, N., Vahteristo, P., Kämpjärvi, K., Arola, J., Bützow, R., & Aaltonen, L. A. (2013). MED12 exon 2 mutations in histopathological uterine leiomyoma variants. European Journal of Human Genetics : EJHG, 21(11), 1300-3. https://doi.org/10.1038/ejhg.2013.33
Mäkinen N, et al. MED12 Exon 2 Mutations in Histopathological Uterine Leiomyoma Variants. Eur J Hum Genet. 2013;21(11):1300-3. PubMed PMID: 23443020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MED12 exon 2 mutations in histopathological uterine leiomyoma variants. AU - Mäkinen,Netta, AU - Vahteristo,Pia, AU - Kämpjärvi,Kati, AU - Arola,Johanna, AU - Bützow,Ralf, AU - Aaltonen,Lauri A, Y1 - 2013/02/27/ PY - 2012/10/11/received PY - 2013/01/18/revised PY - 2013/01/30/accepted PY - 2013/2/28/entrez PY - 2013/2/28/pubmed PY - 2014/5/8/medline SP - 1300 EP - 3 JF - European journal of human genetics : EJHG JO - Eur. J. Hum. Genet. VL - 21 IS - 11 N2 - Uterine leiomyomas, or fibroids, are the most common human tumors. Based on histopathology, they can be divided into common leiomyomas and various relatively rare subtypes that mimic malignancy in one or more aspects. Recently, we showed that exon 2 of mediator complex subunit 12 (MED12) is mutated in up to 70% of common fibroids. To investigate the frequency of MED12 exon 2 mutations in histopathological uterine leiomyoma variants, we screened altogether 206 lesions, including 69 histopathologically common leiomyomas, 59 cellular (23 cellular and 36 highly cellular), 18 atypical and 26 mitotically active leiomyomas, as well as 34 uterine fibroid samples from 14 hereditary leiomyomatosis and renal cell cancer patients with a heterozygous germ line mutation in fumarate hydratase (FH). The uterine leiomyoma variants harbored MED12 exon 2 mutations significantly less frequently than common leiomyomas (P=2.93 × 10(-8)). In all, 6 mutations were detected among cellular fibroids (6/67; 8.96%), 3 among atypical fibroids (3/18; 16.67%) and 10 among mitotically active fibroids (10/26; 38.46%). Only mitotically active fibroids displayed a mutation frequency that was not statistically different from common leiomyomas (P=0.11). Three MED12 exon 2 mutations were detected among 34 tumors with a heterozygous germ line FH mutation (P=5.28 × 10(-7)). None of these tumors displayed biallelic inactivation of FH. Our results suggest that MED12 mutation positivity is a key characteristic of common leiomyomas. Cellular and atypical fibroids, in particular, may arise through different molecular mechanisms. The results also propose that MED12 and biallelic FH mutations may be mutually exclusive. SN - 1476-5438 UR - https://www.unboundmedicine.com/medline/citation/23443020/MED12_exon_2_mutations_in_histopathological_uterine_leiomyoma_variants_ L2 - http://dx.doi.org/10.1038/ejhg.2013.33 DB - PRIME DP - Unbound Medicine ER -