Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer

被引：89

作者：

Kampjarvi, K. ^{[1
]}

Makinen, N. ^{[1
]}

Kilpivaara, O. ^{[1
]}

Arola, J. ^{[2
,3
]}

Heinonen, H-R ^{[1
]}

Bohm, J. ^{[4
]}

Abdel-Wahab, O. ^{[5
]}

Lehtonen, H. J. ^{[1
]}

Pelttari, L. M. ^{[6
,7
]}

Mehine, M. ^{[1
]}

Schrewe, H. ^{[8
]}

Nevanlinna, H. ^{[6
,7
]}

Levine, R. L. ^{[5
]}

Hokland, P. ^{[9
]}

Bohling, T. ^{[2
,3
]}

Mecklin, J-P ^{[10
,11
]}

Butzow, R. ^{[2
,3
]}

Aaltonen, L. A. ^{[1
]}

Vahteristo, P. ^{[1
]}

机构：

[1] Univ Helsinki, Dept Med Genet, Genome Scale Biol Res Program, FIN-00014 Helsinki, Finland

[2] Univ Helsinki, Cent Hosp, Lab Helsinki Univ Cent Hosp HUSLAB, Dept Pathol, FIN-00014 Helsinki, Finland

[3] Univ Helsinki, Haartman Inst, FIN-00014 Helsinki, Finland

[4] Jyvaskyla Cent Hosp, Dept Pathol, FIN-40620 Jyvaskyla, Finland

[5] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[6] Univ Helsinki, Dept Obstet & Gynecol, FIN-00029 Helsinki, Finland

[7] Univ Helsinki, Cent Hosp, FIN-00029 Helsinki, Finland

[8] Max Planck Inst Mol Genet, Dept Dev Genet, D-14195 Berlin, Germany

[9] Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus C, Denmark

[10] Jyvaskyla Cent Hosp, Dept Surg, FIN-40620 Jyvaskyla, Finland

[11] Univ Eastern Finland, FIN-40620 Jyvaskyla, Finland

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 107卷 / 10期

基金：

芬兰科学院;

关键词：

MED12; mutation screening; somatic mutation; benign tumours; malignant tumours; LEIOMYOMAS; REGULATOR; MEDIATOR; CDK8;

D O I：

10.1038/bjc.2012.428

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. British Journal of Cancer (2012) 107, 1761-1765. doi:10.1038/bjc.2012.428 www.bjcancer.com Published online 20 September 2012 (C) 2012 Cancer Research UK

引用

页码：1761 / 1765

页数：5

共 22 条

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