1. Genomics of uterine leiomyomas: insights from high-throughput sequencing 
Miika Mehine, M.Sc., Netta Mäkinen, M.Sc., Hanna-Riikka Heinonen, M.B., Lauri A. Aaltonen, M.D., Ph.D., Pia Vahteristo, Ph.D. 
Fertility and Sterility 
Volume 102, Issue 3, Pages (September 2014)
DOI: /j.fertnstert
Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

2. Figure 1
A schematic representation of the Mediator and the effect of MED12 mutation on its function. (A) Binding of MED12 to Cyclin C activates the CDK8/19 kinase activity and results in phosphorylation of the C-terminal domain of RNA polymerase II. (B) Mutated MED12 has a reduced binding to Cyclin C and results in the loss of the CDK8/19 kinase activity.
Fertility and Sterility  , DOI: ( /j.fertnstert )
Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

3. Figure 2
Complex chromosomal rearrangements (CCRs) resembling chromothripsis in uterine leiomyomas. (A) Chromothripsis is a phenomenon in which one or a few chromosomes are locally shattered and randomly reassembled in a single event. This shattering often leads to the loss of DNA fragments and highly complex chromosomes. (B) The circos plot illustrates rearrangements in a single uterine leiomyoma. Lines between and within chromosomes represent chromosomal rearrangements, and blue boxes represent deleted fragments. A chromothripsis event in this tumor involved chromosomes 6, 8, 12, and 14, and resulted in a rearrangement between HMGA2 and RAD51B.
Figure 2B is from: Mehine et al. Characterization of uterine leiomyomas by whole-genome sequencing, N Engl J Med 369:43–53. Copyright 2013, Massachusetts Medical Society. Reprinted with permission.
Fertility and Sterility  , DOI: ( /j.fertnstert )
Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

4. Figure 3
Several recurrent driver genes have been discovered in uterine leiomyomas. (A) The vast majority of leiomyomas harbor MED12 or HMGA2 aberrations. FH and COL4A5-COL4A6 aberrations appear to be less common. These genetic defects appear to be mutually exclusive and may represent the most important initiators of tumorigenesis. Thus, only a fraction of leiomyomas do not have an identifiable driver mutation. (B) Unsupervised hierarchical clustering analysis of 38 uterine leiomyomas shows that leiomyomas with MED12 mutations, FH inactivation, HMGA2/1 overexpression, and COL4A6-COL4A5 deletion have distinct gene expression profiles.
Figure 3B is modified from: Mehine et al. Characterization of uterine leiomyomas by whole-genome sequencing. N Engl J Med 369:43–53. Copyright 2013, Massachusetts Medical Society. Reprinted with permission.
Fertility and Sterility  , DOI: ( /j.fertnstert )
Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions