HMGI-C and HMGI(Y) Immunoreactivity Correlates with Cytogenetic Abnormalities in Lipomas, Pulmonary Chondroid Hamartomas, Endometrial Polyps, and Uterine Leiomyomas and is Compatible with Rearrangement of the HMGI-C and HMGI(Y) Genes

Abstract

SUMMARY:High-mobility group (HMG) proteins are nonhistone nuclear proteins that play an important role in the regulation of chromatin structure and function. HMGI-C and HMGI(Y) are members of the HMGI family of HMG proteins, and their expression in adult tissues generally correlates with malignant tumor phenotypes. However, HMGI-C and HMGI(Y) dysregulation as a result of specific rearrangements involving 12q15 and 6p21, the respective chromosomal sites in which the HMGI-C and HMGI(Y) genes are located, is also identified in a variety of common benign mesenchymal tumors, such as lipomas and uterine leiomyomata. The general prevalence of HMGI-C and HMGI(Y) protein expression and its correlation with chromosomal alterations in these benign tumors are unknown. We analyzed 95 human tumors (20 lipomas, 21 pulmonary chondroid hamartomas, 26 uterine leiomyomata, and 28 endometrial polyps) representing a selection of the benign lesions in which karyotypic alterations involving the chromosomal regions 12q15 and 6p21 are frequently detected. All cases were successfully karyotyped and some of them analyzed by fluorescent in situ hybridization with probes spanning the HMGI-C and HMGI(Y) genes. The results of this study demonstrate that expression of HMGI-C or HMGI(Y) is a common occurrence in lipomas, pulmonary chondroid hamartomas, leiomyomata, and endometrial polyps; that it correlates with 12q15 and 6p21 chromosomal alterations (p Ͻ 0.001); and that it is compatible with rearrangement of the HMGI-C and HMGI(Y) genes. The expression pattern and cellular localization of the immunoreactivity support the view that in biphasic lesions composed of a mixture of both stromal and epithelial cells, such as pulmonary chondroid hamartoma and endometrial polyps, the mesenchymal component is the site of the HMGI genetic alterations. (Lab Invest 2000, 80:359-369).

Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

“…Alteration of human mobility group protein genes caused by the gene translocation (chromosomal reciprocal translocations) are also considered candidate genes for leiomyomata. 3,5 In this study, we evaluated the role of tuberin, insulin-signaling, steroid receptor cofactors as well as high-mobility group protein gene A2 in the leiomyomata. Based on the information obtained from animal model Eker rat (Tsc2 Ek/ þ ), which carries one wild-type allele of the tuberous sclerosis gene 2 and one allele containing an inactivating viral insertion in intron 30, loss of tuberous sclerosis gene 2 is closely associated with the development of leiomyomata.…”

“…6,38,39 The causal relation between changes in these high mobility group protein genes and aberrant growth control in benign tumors remains to be established. 3 Tallini et al 5 found that about 36% (9/25) of leiomyomata presented chromosomal alteration involving chromosome 12, near high-mobility group protein gene A2 locus. Those cases with altered chromosome 12 showed an upregulation of high-mobility group protein gene A2 in 50% of cases.…”

“…5,6 In our study, we examined highmobility group protein gene A2 in terms of its association with other proteins. Differential expression of high-mobility group protein gene A2 was noted in 26 out of 56 cases (46.4%).…”

“…3,4 The high-mobility group protein genes are considered candidate genes for leiomyomata as these were identified from breakpoints of chromosomal translocation in leiomyomata. 3,5 Although an upregulation of high-mobility group protein gene A2 has been found in some leiomyomata, 5,6 the fusion highmobility group protein gene A2 by truncated transcripts at translocation breakpoints is not a common molecular event. 7 Gene chip studies have provided a means of identifying differentially expressed genes in leiomyomata.…”

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

“…[20][21][22][23][24][25][26][27][28][29][30][31][32] The putative oncogene, HMGIY (high mobility group protein isoforms I and Y), localized to 6p21 has been proposed to play a role in the development of a number of these neoplasms. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] An identical t(17;17)(q12;p13) was seen in two previous studies. 7,9 Interestingly, an inversion of chromosome 17 [inv(17)(p13q11.2-12)] involving similar breakpoints was observed in case 37 of the present study (Figure 3).…”