Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer

Br J Cancer. 2012 Nov 6;107(10):1761-5. doi: 10.1038/bjc.2012.428. Epub 2012 Sep 20.


Background: Mediator complex participates in transcriptional regulation by connecting regulatory DNA sequences to the RNA polymerase II initiation complex. Recently, we discovered through exome sequencing that as many as 70% of uterine leiomyomas harbour specific mutations in exon 2 of mediator complex subunit 12 (MED12). In this work, we examined the role of MED12 exon 2 mutations in other tumour types.

Methods: The frequency of MED12 exon 2 mutations was analysed in altogether 1158 tumours by direct sequencing. The tumour spectrum included mesenchymal tumours (extrauterine leiomyomas, endometrial polyps, lipomas, uterine leiomyosarcomas, other sarcomas, gastro-intestinal stromal tumours), hormone-dependent tumours (breast and ovarian cancers), haematological malignancies (acute myeloid leukaemias, acute lymphoid leukaemias, myeloproliferative neoplasms), and tumours associated with abnormal Wnt-signalling (colorectal cancers (CRC)).

Results: Five somatic alterations were observed: three in uterine leiomyosarcomas (3/41, 7%; Gly44Ser, Ala38_Leu39ins7, Glu35_Leu36delinsVal), and two in CRC (2/392, 0.5%; Gly44Cys, Ala67Val).

Conclusion: Somatic MED12 exon 2 mutations were observed in uterine leiomyosarcomas, suggesting that a subgroup of these malignant tumours may develop from a leiomyoma precursor. Mutations in CRC samples indicate that MED12 may, albeit rarely, contribute to CRC tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Exome
  • Exons
  • Female
  • Humans
  • Leiomyoma / genetics
  • Leiomyoma / pathology
  • Leiomyosarcoma / genetics*
  • Leiomyosarcoma / pathology
  • Mediator Complex / genetics*
  • Mutation
  • Sequence Analysis, DNA / methods
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / pathology


  • MED12 protein, human
  • Mediator Complex