Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer

• Published in: British journal of cancer Vol. 107; no. 10; pp. 1761 - 1765
• Main Authors: Kämpjärvi, K, Mäkinen, N, Kilpivaara, O, Arola, J, Heinonen, H-R, Böhm, J, Abdel-Wahab, O, Lehtonen, H J, Pelttari, L M, Mehine, M, Schrewe, H, Nevanlinna, H, Levine, R L, Hokland, P, Böhling, T, Mecklin, J-P, Bützow, R, Aaltonen, L A, Vahteristo, P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.11.2012; Nature Publishing Group
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Drug Resistance; Epidemiology; Exome; Exons; Female; Female genital diseases; Fibroids; Genes; Genetics; Gynecology. Andrology. Obstetrics; Hematology; Humans; Kinases; Leiomyoma - genetics; Leiomyoma - pathology; Leiomyosarcoma - genetics; Leiomyosarcoma - pathology; Leukemia; Mediator Complex - genetics; Medical research; Medical sciences; Molecular Medicine; Mutation; Oncology; Ovaries; Proteins; RNA polymerase; Sarcoma; Sequence Analysis, DNA - methods; Short Communication; Transcription factors; Tumorigenesis; Tumors; Uterine Neoplasms - genetics; Uterine Neoplasms - pathology; Denmark; Aarhus Denmark; Finland; mutation screening; malignant tumours; benign tumours; somatic mutation; Uterine leiomyosarcoma; Rectal disease; Colorectal cancer; Uterus cancer; Malignant tumor; Medical screening; Female genital diseases; Colonic disease; Somatic mutation; MED12; Cancerology; Uterine diseases; Digestive diseases; Intestinal disease; Genetics; Benign neoplasm; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.428

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.