Novel MED12 gene somatic mutations in women from the Southern United States with symptomatic uterine fibroids

Sunil K. Halder, Archana Laknaur, Jessica Miller, Lawrence C. Layman, Michael Diamond, Ayman Al-Hendy

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)505-511
Number of pages7
JournalMolecular Genetics and Genomics
Volume290
Issue number2
DOIs
StatePublished - Mar 17 2015

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Mediator Complex
Leiomyoma
Mutation
Genes
Exons
Myometrium
Sequence Deletion
South America
Finland
North America
South Africa

Keywords

  • Leiomyoma
  • MED12
  • Pathogenesis
  • Somatic mutations
  • Uterine fibroids

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Novel MED12 gene somatic mutations in women from the Southern United States with symptomatic uterine fibroids. / Halder, Sunil K.; Laknaur, Archana; Miller, Jessica; Layman, Lawrence C.; Diamond, Michael; Al-Hendy, Ayman.

In: Molecular Genetics and Genomics, Vol. 290, No. 2, 17.03.2015, p. 505-511.

Research output: Contribution to journalArticle

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title = "Novel MED12 gene somatic mutations in women from the Southern United States with symptomatic uterine fibroids",
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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AB - 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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