MED12 exon 2 mutations are common in uterine leiomyomas from South African patients

Abstract

Uterine leiomyomas, or fibroids, are extremely common tumors. Regardless of their benign nature, fibroids can cause considerable morbidity. Women with African ancestry have a threefold increased risk of developing uterine leiomyomas with a greater symptom severity when compared to white women. Recently, we demonstrated that exon 2 of the MED12 gene is somatically altered in up to 70 per cent of uterine leiomyomas in a series of Finnish (Caucasian) patients. To validate these results in other populations, we sequenced a set of 28 uterine leiomyomas for MED12 exon 2 mutations from 18 different Black African or Coloured South African patients. We observed 14 mutation positive lesions (50%). When corrected by tumor size, these results are very similar to those derived in the Finnish material. This study confirms a major role of MED12 in the genesis of leiomyomas, regardless of ethnicity.

MED12 mutation in patients with hysteromyoma

“…Further studies must be performed to clarify this matter. In addition, the results of the present study also showed that the MED12 mutation frequency in small hysteromyomas was higher than that in large hysteromyomas, which was consistent with the study by Mäkinen et al (7).…”

“…The reported mutation frequency in the South African population appeared to be lower than that found in Caucasian individuals, which may be a result of the size of the hysteromyoma in these patients. The tumors of the individuals of the South African population were usually large, and according the study by Mäkinen et al, the size of the hysteromyoma may be negatively correlated with the presence of mutations (7). In the present study, the mutation frequency of MED12 in hysteromyoma was 54.39%, similar to that of the individuals of African descent, and lower than that of the Finnish or North American populations.…”

“…Previous studies have shown that the second exon of the MED12 gene in hysteromyoma patients who were from Finland, North America or South Africa presented with high mutation frequencies (7)(8)(9). The reported mutation frequency in the South African population appeared to be lower than that found in Caucasian individuals, which may be a result of the size of the hysteromyoma in these patients.…”

“…Certain recent studies have shown that MED12 presents with different mutations frequencies in hysteromyoma patients of different racial populations (7)(8)(9), which suggests that MED12 mutations have an important role in causing hysteromyoma. At present, there is no study with regard to MED12 gene mutations in hysteromyoma patients of the Chinese Han population.…”

MED12 mutations in human diseases

“…It has been reported that in patients suffering from uterine leiomyoma, MED12 mutations are found in stem cells, which leads to unlimited growth and tumor. The mutation sites in MED12 are located in the second exon (Makinen et al, 2011a(Makinen et al, , 2011bJe et al, 2012;Markowski et al, 2012). It was recently reported that the second exon mutation occurs in 52.2% of uterine fi broid patients while the mutation is not found in other tumors (Je et al, 2012), implicating the involvement of MED12 in the disease.…”