PMC4604635_01
Cytogenetic and molecular analysis of uterine leiomyomas. a-d representative G-banded karyotypes of four uterine leiomyomas. a tumor 709/1, Karyotype: 45,XX,del(3)(q24q25.33),del(7)(q11.2),add(9)(q34),-15,der(17)t(15;17)(q?22;p?11.2)[3]/46,XX[3]. Of ten additional hypodiploid metaphases seven showed structural abnormalities and losses and three only losses of chromosomes. In contrast to the structural abnormalities, none of the losses observed were clonal. b tumor 709/2, karyotype: 43 ~ 46,XX,del(1)(p34),der(2),-11 + mar. c tumor 709/3, karyotype: 46,XX[22]. d tumor 709/4, karyotype: 46,XX[17]. e mutation of MED12 (c.131G > A) of tumor 709/2
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Fig1
Fig. 1a-d, Additional file 1: Table S1) and one of the UL tumors carried a MED12 mutation (709/2. c.131G > A, Fig. 1e). Both shared cytogenetic abnormalities that thus can be considered being clonal (Fig. 1).
Results of CNV-array-analyses. Whole genome views of four uterine leiomyomas investigated. The weihghted log2 ratio of the probes are displayed as colored dots, the smooth signal (Gaussian smoothed calibrated copy number estimate) is displayed as blue line. a tumor 709/1. b tumor 709/2. c tumor 709/3. d tumor 709/4
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Fig2
In contrast to the results obtained by G-banding, the CNV arrays revealed more or less gross genomic alteration in all four UL tumors (Fig. 2) that in neither of the UL tumors could have escaped detection by G-banding.
Rearrangements of chromosome 12 and deletions of the long arm of chromosome 3. a losses of parts of chromosome 12 in tumors 709/3 and 709/4. Black arrowheads indicate the region enlarged in (b). b. position of the HMGA2 gene with intron/exon structure as indicated in a. c. Position of interstitial deletions of the long arm of chromosome 3 in tumors 709/1 and 709/2, respectively. The grey line and a black arrowhead indicate the position of the MED12L gene
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Fig3
E.g., in two UL tumors losses within the close surrounding of or within the HMGA2 locus point to rearrangements of this gene (Fig. 3a, b). Of these, a short 5'proximal deletion mapped outside the putative transcription start of the gene removing a segment of only approximately 280 kbp (Fig. 3a). From the array results it cannot even be ruled out that by this deletion part of the exons 1 and 2 of the gene had been removed (Fig. 3b). Of note, the deleted segments in both UL tumors caused a removal of the gene encoding MED12L (Fig. 3c).
Expression of HMGA2 mRNA in fibroid 709/3 as compared to ten other arbitrarily chosen fibroids without cytogenetically detectable rearrangements of chromosomal region 12q14-15 (white columns) as well as to 19 fibroids that showed a microscopically visible rearrangement of this chromosomal segment (grey columns), respectively
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Fig4
HMGA2 mRNA expression analysis carried out in this case revealed a slightly elevated expression compared to other UL without clonal cytogenetic abnormalities but was clearly lower than in cases with cytogenetically apparent rearrangement of the 12q14-15 region (Fig. 4).