An endometrial polyp with a rearrangement of HMGI-C underlying a complex cytogenetic rearrangement involving chromosomes 2 and 12

Bol, Silvia; Wanschura, S.; Thode, Brita; Deichert, U.; Ven, Wim J.M. Van de; Bartnitzke, Sabine; Bullerdiek, Jörn

doi:10.1016/0165-4608(96)00062-3

Cited by 48 publications

(28 citation statements)

References 10 publications

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“…Rearrangements of the HMGA2 gene have been frequently detected in human benign tumours of mesenchymal origin, including lipomas, pulmonary hamartomas, uterine leiomyomas, endometrial polyps and ®broadenomas of the breast Bol et al, 1996;Kazmierczak et al, 1995;Schoenmakers et al, 1995;Staats et al, 1996). 12q13 ± 15 chromosomal translocations involving the HMGA2 gene locus, account for these rearrangements.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas

et al. 2002

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Overexpression of the HMGA2 gene is a common feature of neoplastic cells both in experimental and human models. Intragenic and extragenic HMGA2 rearrangements responsible for HMGA2 gene overexpression have been frequently detected in human benign tumours of mesenchymal origin. To better understand the role of HMGA2 overexpression in human tumorigenesis, we have generated transgenic mice carrying the HMGA2 gene under the transcriptional control of the cytomegalovirus promoter. High expression of the transgene was demonstrated in all the mouse tissues analysed, whereas no expression of the endogenous HMGA2 gene was detected in the same tissues from wild-type mice. In this study, two indipendent lines of transgenic mice have been generated. By 6 months of age, 85% of female animals of both transgenic lines developed pituitary adenomas secreting prolactin and growth hormone. The transgenic males developed the same phenotype with a lower penetrance (40%) and a longer latency period (about 18 months). Therefore, these data demonstrate that the overexpression of HMGA2 leads to the onset of mixed growth hormone/ prolactin cell pituitary adenomas. These transgenic mice may represent an important tool for the study of this kind of neoplasia.

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Section: Introductionmentioning

confidence: 99%

Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas

et al. 2002

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“…Interestingly, HMGA2 rearrangement or amplification has been implicated in some endometrial polyps. 31,32 Therefore, the finding of frequent HMGA2 amplification and overexpression in adenosarcoma perhaps provides a possible tumorigenic link between both of these benign and malignant counterparts of polypoid endometrial mesenchymal tumors.…”

Section: Discussionmentioning

confidence: 99%

Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup

Lee

Changou

et al. 2016

Modern Pathology

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Müllerian adenosarcomas are malignant gynecologic neoplasms. Advanced staging and sarcomatous overgrowth predict poor prognosis. Because the genomic landscape remains poorly understood, we conducted this study to characterize the genomewide copy number variations in adenosarcomas. Sixteen tumors, including eight with and eight without sarcomatous overgrowth, were subjected to a molecular inversion probe array analysis. Copy number variations, particularly losses, were significantly higher in cases with sarcomatous overgrowth. Frequent gains of chromosomal 12q were noted, often involving cancer-associated genes CDK4 (six cases), MDM2, CPM, YEATS4, DDIT3, GLI1 (five each), HMGA2 and STAT6 (four), without association with sarcomatous overgrowth status. The most frequent losses involved chromosomes 13q (five cases), 9p, 16q and 17q (four cases each) and were almost limited to cases with sarcomatous overgrowth. MDM2 and CDK4 amplification, as well as losses of RB1 (observed in two cases) and CDKN2A/B (one case), was verified by FISH. By immunohistochemistry, all MDM2/CDK4-coamplified cases were confirmed to overexpress both encoded proteins, whereas all four cases with (plus an additional four without) gain of HMGA2 overexpressed the HMGA2 protein. Both cases with RB1 loss were negative for the immunostaining of the encoded protein. Chromothripsis-like copy number profiles involving chromosome 12 or 14 were observed in three fatal cases, all of which harbored sarcomatous overgrowth. With whole chromosome painting and deconvolution fluorescent microscopy, dividing tumor cells in all three cases were shown to have scattered extrachromosomal materials derived from chromosomes involved by chromothripsis, suggesting that this phenomenon may serve as visual evidence for chromothripsis in paraffin

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“…Wild-type HMGA2 has been reported to be overexpressed in various malignant tumors, such as breast cancer (11) and pancreatic tumors (12). In contrast to the overexpression of wild-type HMGA2 in malignant tumors, the HMGA2 gene is rearranged in a variety of benign solid tumors mainly of mesenchymal origin, such as lipomas (13)(14)(15), uterine leiomyomas (13), pleomorphic adenomas of the salivary glands (13), endometrial polyps (16), fibroadenomas of the breast (17), and pulmonary chondroid hamartomas (13,18). Most of these HMGA2 rearrangements have chromosomal breakpoints within the large third intron of the gene, resulting in chimeric transcripts containing exons 1 to 3 of HMGA2 fused to limited ectopic sequences of other genes and encoding more or less a truncated form of HMGA2 comprising its three DNA-binding domains.…”

Section: Introductionmentioning

confidence: 99%

Transactivation Functions of the Tumor-Specific HMGA2/LPP Fusion Protein Are Augmented by Wild-Type HMGA2

Crombez

Vanoirbeek

Ven

et al. 2005

Molecular Cancer Research

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The gene encoding the architectural transcription factor HMGA2 is frequently rearranged in several benign tumors of mesenchymal origin. The lipoma preferred partner (LPP) gene is the most frequent translocation partner of HMGA2 in a subgroup of lipomas, which are benign tumors of adipose tissue. In these lipomas, HMGA2/LPP fusion transcripts are expressed, which encode for the three AT-hooks of HMGA2 followed by the two most carboxyl-terminal LIM domains (protein-protein interaction domains) of LPP. Identical fusion transcripts are also expressed in other benign mesenchymal tumors. Previous studies revealed that the LIM domains of LPP have transcriptional activation capacity in GAL4-based luciferase reporter assays. Here, we show that the HMGA2/LPP fusion protein retains the transactivation functions of the LPP LIM domains and thus functions as transcription factor. The HMGA2/LPP fusion protein activates transcription from the well-characterized PRDII element, which is a part of the IFN-B B enhancer and which is known to bind to HMGA2. We also show that HMGA2/LPP activates transcription from the BAT-1 element of the rhodopsin promoter, a HMGA1-binding element. HMGA1 is a closely related family member of HMGA2. Finally, in a number of lipomas, HMGA2/LPP and HMGA2 are coexpressed, and HMGA2 augments the transactivation functions of HMGA2/LPP. These results support the concept that the transactivation functions of the novel HMGA2/LPP transcription factor contribute to lipomagenesis.

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An endometrial polyp with a rearrangement of HMGI-C underlying a complex cytogenetic rearrangement involving chromosomes 2 and 12

Cited by 48 publications

References 10 publications

Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas

Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas

Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup

Transactivation Functions of the Tumor-Specific HMGA2/LPP Fusion Protein Are Augmented by Wild-Type HMGA2

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