Somatic MED12 Mutations in Uterine Leiomyosarcoma and Colorectal Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2012 Nov 8

PMID 23132392

Citations 50

Authors

K Kampjarvi

N Makinen

O Kilpivaara

J Arola

H-R Heinonen

J Bohm

O Abdel-Wahab

H J Lehtonen

L M Pelttari

M Mehine

H Schrewe

H Nevanlinna

R L Levine

P Hokland

T Bohling

J-P Mecklin

R Butzow

L A Aaltonen

P Vahteristo

Affiliations

Soon will be listed here.

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.

Citing Articles

Therapeutic targeting of the tryptophan-kynurenine-aryl hydrocarbon receptor pathway with apigenin in MED12-mutant leiomyoma cells.

Iizuka T, Zuberi A, Wei H, Coon V J, Anton M, Buyukcelebi K Cancer Gene Ther. 2025; .

PMID: 40025195 DOI: 10.1038/s41417-025-00881-0.

Advancement in Multi-omics approaches for Uterine Sarcoma.

Wang W, Hu Y, Fu F, Ren W, Wang T, Wang S Biomark Res. 2024; 12(1):129.

PMID: 39472980 PMC: 11523907. DOI: 10.1186/s40364-024-00673-y.

Comprehensive mutational profiling identifies new driver events in cutaneous leiomyosarcoma.

van der Weyden L, Del Castillo Velasco-Herrera M, Cheema S, Wong K, Boccacino J, Offord V Br J Dermatol. 2024; 192(2):335-343.

PMID: 39392932 PMC: 11758588. DOI: 10.1093/bjd/ljae386.

Engineered MED12 mutations drive leiomyoma-like transcriptional and metabolic programs by altering the 3D genome compartmentalization.

Buyukcelebi K, Chen X, Abdula F, Elkafas H, Duval A, Ozturk H Nat Commun. 2023; 14(1):4057.

PMID: 37429859 PMC: 10333368. DOI: 10.1038/s41467-023-39684-y.

Engineered MED12 mutations drive uterine fibroid-like transcriptional and metabolic programs by altering the 3D genome compartmentalization.

Buyukcelebi K, Chen X, Abdula F, Duval A, Ozturk H, Seker-Polat F Res Sq. 2023; .

PMID: 36798375 PMC: 9934745. DOI: 10.21203/rs.3.rs-2537075/v1.

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