Abstract
Although somatic mutations in exon 2 of the mediator complex subunit 12 (MED12) gene have been reported previously in uterine fibroids in women from Finland, South Africa, and North America, the status of these mutations was not reported in the Southern United States women. The aim of this study is to determine the MED12 somatic mutations in uterine fibroids of women from Southern Unites States, which will help to better understand the contribution of MED12 mutations in fibroid tumor biology. Herein, we determined the frequency of MED12 gene exon 2 somatic mutations in 143 fibroid tumors from a total of 135 women from the Southern United States and in 50 samples of the adjacent myometrium using PCR amplification and Sanger sequencing. We observed that the MED12 gene is mutated in 64.33 % (92/143) of uterine fibroid cases in the exon 2 (including deletion mutations). These mutations include 107T > G (4.3 %), 130G > C (2.8 %), 130G > A (7.0 %), 130G > T (2.8 %), 131G > C (2.1 %), 131G > A (20.2 %), and 131G > T (2.1 %). Interestingly, we identified four novel mutations in these patients: 107 T > C (12.8 %), 105A > T (2.1 %), 122T > A (2.1 %), and 92T > A (2.1 %). As expected, we did not observe any mutations in the normal myometrium. Moreover, we found a higher rate of deletion mutations (17.5 %, 25/143) in the above fibroid tumors. Our results clearly demonstrate that the MED12 gene exon 2 is frequently mutated in human uterine fibroids in Southern United States women. These results highlight the molecular pathogenesis of human uterine fibroids with the central role of MED12 somatic mutations.
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Acknowledgments
We would like to thank the Vanderbilt DNA core facility for custom sequencing of exon 2 of the MED12 gene. This study was supported primarily by the Research Centers in Minority Institutions (RCMI) pilot grant 2G12RR003032-26 (to S. K. H), and National Institute of Health (NIH)/R01 HD046228 (to A. A. H.).
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The authors in this paper have no conflict of interest or nothing to disclose.
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Communicated by S. Hohmann.
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438_2014_938_MOESM1_ESM.docx
Supplemental data (Figure 1). MED12 genomic mutations. Sequence chromatographs showing common somatic mutations in the MED12 codon 44 in human uterine fibroids. Sequences were viewed using FinchTV software provided by the Vanderbilt University. Examples of genomic DNA sequencing traces in codon 44-mutated uterine fibroid samples and a wild-type myometrium sample adjacent to uterine fibroid are shown. Codon 44 is highlighted by the horizontal bars, as indicated. Mutated bases in the codon 44 are indicated by arrows (DOCX 8785 kb)
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Halder, S.K., Laknaur, A., Miller, J. et al. Novel MED12 gene somatic mutations in women from the Southern United States with symptomatic uterine fibroids. Mol Genet Genomics 290, 505–511 (2015). https://doi.org/10.1007/s00438-014-0938-x
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DOI: https://doi.org/10.1007/s00438-014-0938-x