For wild-type HMGA2 to evaluate whether PLAG1 can be transcriptionally activated by HMGA2. Previous studies on pleomorphic adenomas of the salivary glands have shown that PLAG1 is frequently overexpressed in PASG with normal karyotype as well as with 12q14,15 abnormalities. Akin to what has been described for PASG, the results of the present study indicate that both genes are co-expressed in thyroid tumors as well as in leiomyomas. In papillary carcinomas, both genes are expressed at higher levels than in follicular adenomas. Follicular carcinomas with high HMGA2 expression levels also express PLAG1 at elevated levels. A Z-VAD-FMK 187389-52-2 correlation between chromosomal rearrangements affecting the HMGA2 locus and the HMGA2 protein expression has been shown in uterine leiomyomas. Moreover, it has been shown that in thyroid carcinomas the increased expression of HMGA2 and PLAG1 is detectable on the mRNA as well as on the protein level. Therefore, the correlation of HMGA2 and PLAG1 mRNA expression described herein is expected to reflect a correlation at the protein level as well. Besides the typical rearrangements involving chromosomal band 8q12 including the most frequent t, an activation of PLAG1 in pleomorphic adenomas of the salivary glands occurs also in tumors with 12q14,15 abnormalities lacking 8q12 aberrations. Besides 13/17 tumors with an apparently normal karyotype, 5/10 pleomorphic adenomas with 12q13,15 abnormalities were found to overexpress PLAG1. In the same study, the PLAG1 expression was investigated in three UL, and two cases were also found to overexpress PLAG1, but no cytogenetic data were available for these three tumors. These findings suggest alternative mechanisms of PLAG1 activation in tumorigenesis other than gene rearrangements. The results presented herein point to HMGA2 as an upstream regulator of PLAG1 and are additionally confirmed by the correlation between the expressions of both genes in uterine leiomyomas. An activation of HMGA2 in UL by 12q14 aberrations is well known. Therefore, we chose 15 UL with an apparently normal karyotype or with chromosomal aberrations affecting regions other than 12q14 and 17 cases with 12q14 aberrations to quantify the expression of PLAG1 and HMGA2 simultaneously. Of the 15 UL showing low HMGA2 levels, 13 also showed low levels of PLAG1. The two remaining cases showed an elevated PLAG1 expression despite a low HMGA2 mRNA expression, thus pointing to mechanisms other than HMGA2 upregulation being responsible for PLAG1 activation. In pleomorphic adenomas of the salivary gland cryptic, intrachromosomal 8q rearrangements have been observed leading to a fusion of PLAG1 with CHCHD7 or TCEA1. Because the breakpoints are located in the 59-noncoding regions of both fusion partners, these fusions lead to an activation of PLAG1 by promoter swapping. Similar events that escape detection by conventional cytogenetics may have caused the upregulation of PLAG1 observed in two UL without visible rearrangements affecting 8q12. In all 17 UL with elevated HMGA2 levels a concomitant overexpression of PLAG1 was noted.