Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer Journal Article

   


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.; Butzow, R.; Aaltonen, L. A.; Vahteristo, P.
Article 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).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. © 2012 Cancer Research UK. All rights reserved.
Keywords: somatic mutation; benign tumours; malignant tumours; med12; mutation screening
Journal Title: British Journal of Cancer
Volume: 107
Issue: 10
ISSN: 0007-0920
Publisher: Nature Publishing Group  
Date Published: 2012-11-06
Start Page: 1761
End Page: 1765
Language: English
DOI: 10.1038/bjc.2012.428
PROVIDER: scopus
PMCID: PMC3493861
PUBMED: 23132392
DOI/URL:

http://release-www.scopus.com/inward/record.url?eid=2-s2.0-84869029053&partnerID=40&md5=7a6d09fdfbd78f3ab1a7e656c42529c9
Notes: --- - "Export Date: 3 December 2012" - "CODEN: BJCAA" - "Source: Scopus"
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MSK Authors
  1. Ross Levine
    782 Levine
  2. Omar Ibrahim Abdel-Wahab
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