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Exomic landscape of MED12 mutation-negative and -positive uterine leiomyomas.
Int J Cancer. 2014 Feb 15; 134(4):1008-12.IJ

Abstract

Uterine leiomyomas are extremely common tumors originating from the smooth muscle cells of myometrium. We recently reported recurrent somatic mutations in mediator complex subunit 12 (MED12) in the majority of these lesions, and analyzed chromosomal abnormalities in leiomyomas by whole-genome sequencing. The aim of our study was to examine in detail uterine leiomyoma exomes, to search for driver mutations in MED12 mutation-negative leiomyomas and to scrutinize MED12 mutation-positive leimyomas for additional contributing mutations. We analyzed whole exome sequencing data of 27 uterine leiomyomas (12 MED12 mutation-negative and 15 MED12 mutation-positive) and their paired normal myometrium. We searched for genes, which would be recurrently mutated. No such genes were identified in MED12 mutation-negative uterine leiomyomas. Similarly, MED12 mutation-positive leiomyomas displayed no additional recurrent changes. The complete lack of novel driver point mutations in the examined series highlights the unique role of MED12 mutations in genesis of uterine leiomyomas, and suggests that these mutations alone may be sufficient for tumor development. Additional factors that cannot be detected by exome sequencing, such as somatic structural rearrangements, epigenetic events and intronic variants, are likely to have a particular impact to the development of MED12 wild-type lesions.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

23913526

Citation

Mäkinen, Netta, et al. "Exomic Landscape of MED12 Mutation-negative and -positive Uterine Leiomyomas." International Journal of Cancer, vol. 134, no. 4, 2014, pp. 1008-12.
Mäkinen N, Vahteristo P, Bützow R, et al. Exomic landscape of MED12 mutation-negative and -positive uterine leiomyomas. Int J Cancer. 2014;134(4):1008-12.
Mäkinen, N., Vahteristo, P., Bützow, R., Sjöberg, J., & Aaltonen, L. A. (2014). Exomic landscape of MED12 mutation-negative and -positive uterine leiomyomas. International Journal of Cancer, 134(4), 1008-12. https://doi.org/10.1002/ijc.28410
Mäkinen N, et al. Exomic Landscape of MED12 Mutation-negative and -positive Uterine Leiomyomas. Int J Cancer. 2014 Feb 15;134(4):1008-12. PubMed PMID: 23913526.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exomic landscape of MED12 mutation-negative and -positive uterine leiomyomas. AU - Mäkinen,Netta, AU - Vahteristo,Pia, AU - Bützow,Ralf, AU - Sjöberg,Jari, AU - Aaltonen,Lauri A, Y1 - 2013/08/29/ PY - 2013/05/08/received PY - 2013/07/12/accepted PY - 2013/8/6/entrez PY - 2013/8/6/pubmed PY - 2014/2/22/medline KW - MED12 KW - exome sequencing KW - fibroid KW - uterine leiomyoma SP - 1008 EP - 12 JF - International journal of cancer JO - Int. J. Cancer VL - 134 IS - 4 N2 - Uterine leiomyomas are extremely common tumors originating from the smooth muscle cells of myometrium. We recently reported recurrent somatic mutations in mediator complex subunit 12 (MED12) in the majority of these lesions, and analyzed chromosomal abnormalities in leiomyomas by whole-genome sequencing. The aim of our study was to examine in detail uterine leiomyoma exomes, to search for driver mutations in MED12 mutation-negative leiomyomas and to scrutinize MED12 mutation-positive leimyomas for additional contributing mutations. We analyzed whole exome sequencing data of 27 uterine leiomyomas (12 MED12 mutation-negative and 15 MED12 mutation-positive) and their paired normal myometrium. We searched for genes, which would be recurrently mutated. No such genes were identified in MED12 mutation-negative uterine leiomyomas. Similarly, MED12 mutation-positive leiomyomas displayed no additional recurrent changes. The complete lack of novel driver point mutations in the examined series highlights the unique role of MED12 mutations in genesis of uterine leiomyomas, and suggests that these mutations alone may be sufficient for tumor development. Additional factors that cannot be detected by exome sequencing, such as somatic structural rearrangements, epigenetic events and intronic variants, are likely to have a particular impact to the development of MED12 wild-type lesions. SN - 1097-0215 UR - https://www.unboundmedicine.com/medline/citation/23913526/Exomic_landscape_of_MED12_mutation_negative_and__positive_uterine_leiomyomas_ L2 - https://doi.org/10.1002/ijc.28410 DB - PRIME DP - Unbound Medicine ER -