title: Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, PO Box 63, Helsinki FIN-00014, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Kämpjärvi
authors.forename: N
authors.initials: N
authors.lastname: Mäkinen
authors.forename: O
authors.initials: O
authors.lastname: Kilpivaara
authors.forename: J
authors.initials: J
authors.lastname: Arola
authors.forename: H-R
authors.initials: HR
authors.lastname: Heinonen
authors.forename: J
authors.initials: J
authors.lastname: Böhm
authors.forename: O
authors.initials: O
authors.lastname: Abdel-Wahab
authors.forename: H J
authors.initials: HJ
authors.lastname: Lehtonen
authors.forename: L M
authors.initials: LM
authors.lastname: Pelttari
authors.forename: M
authors.initials: M
authors.lastname: Mehine
authors.forename: H
authors.initials: H
authors.lastname: Schrewe
authors.forename: H
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: R L
authors.initials: RL
authors.lastname: Levine
authors.forename: P
authors.initials: P
authors.lastname: Hokland
authors.forename: T
authors.initials: T
authors.lastname: Böhling
authors.forename: J-P
authors.initials: JP
authors.lastname: Mecklin
authors.forename: R
authors.initials: R
authors.lastname: Bützow
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: P
authors.initials: P
authors.lastname: Vahteristo
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D059472:Exome; D005091:Exons; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000473:pathology; D007890:Leiomyosarcoma / Q000235:genetics* / Q000473:pathology; D056892:Mediator Complex / Q000235:genetics*; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex