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Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer.
Br J Cancer. 2012 Nov 06; 107(10):1761-5.BJ

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.

Authors+Show Affiliations

Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, PO Box 63, Helsinki FIN-00014, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23132392

Citation

Kämpjärvi, K, et al. "Somatic MED12 Mutations in Uterine Leiomyosarcoma and Colorectal Cancer." British Journal of Cancer, vol. 107, no. 10, 2012, pp. 1761-5.
Kämpjärvi K, Mäkinen N, Kilpivaara O, et al. Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer. Br J Cancer. 2012;107(10):1761-5.
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. (2012). Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer. British Journal of Cancer, 107(10), 1761-5. https://doi.org/10.1038/bjc.2012.428
Kämpjärvi K, et al. Somatic MED12 Mutations in Uterine Leiomyosarcoma and Colorectal Cancer. Br J Cancer. 2012 Nov 6;107(10):1761-5. PubMed PMID: 23132392.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer. AU - Kämpjärvi,K, AU - Mäkinen,N, AU - Kilpivaara,O, AU - Arola,J, AU - Heinonen,H-R, AU - Böhm,J, AU - Abdel-Wahab,O, AU - Lehtonen,H J, AU - Pelttari,L M, AU - Mehine,M, AU - Schrewe,H, AU - Nevanlinna,H, AU - Levine,R L, AU - Hokland,P, AU - Böhling,T, AU - Mecklin,J-P, AU - Bützow,R, AU - Aaltonen,L A, AU - Vahteristo,P, Y1 - 2012/09/20/ PY - 2012/11/8/entrez PY - 2012/11/8/pubmed PY - 2013/4/2/medline SP - 1761 EP - 5 JF - British journal of cancer JO - Br. J. Cancer VL - 107 IS - 10 N2 - 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. SN - 1532-1827 UR - https://www.unboundmedicine.com/medline/citation/23132392/Somatic_MED12_mutations_in_uterine_leiomyosarcoma_and_colorectal_cancer_ L2 - http://dx.doi.org/10.1038/bjc.2012.428 DB - PRIME DP - Unbound Medicine ER -