Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours

Schoenmakers, Eric; Wanschura, S.; Mols, Raf; Bullerdiek, Jörn; Berghe, Herman Van den; Ven, Wim J.M. Van de

doi:10.1038/ng0895-436

Cited by 522 publications

(461 citation statements)

References 36 publications

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“…This analysis identified several candidate genes, but we put our attention on Hmga2 (Figure 6a), another member of HMGA family, which maps on chromosome 12q13-15 and is causally involved in a variety of benign and malignant tumors Schoenmakers et al, 1995;Fedele et al, 2001;Fusco and Fedele, 2007). To better investigate the influence of miR-196a-2 on Hmga2 expression, we searched for changes in HMGA2 protein and mRNA levels in NIH3T3 cells transfected with the miR-196a-2 precursor (miR-196a-2) or its No significant changes in the HMGA2 mRNA levels were observed in the cells transfected with the miR196a-2 or its inhibitors (Figure 6d).…”

Section: Mir-196a-2 Downregulates Hmga2mentioning

confidence: 99%

Regulation of microRNA expression by HMGA1 proteins

et al. 2009

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The High Mobility Group proteins HMGA1 are nuclear architectural factors that play a critical role in a wide range of biological processes. Since recent studies have identified the microRNAs (miRNAs) as important regulators of gene expression, modulating critical cellular functions such as proliferation, apoptosis and differentiation, the aim of our work was to identify the miRNAs that are physiologically regulated by HMGA1 proteins. To this purpose, we have analysed the miRNA expression profile of mouse embryonic fibroblasts (MEFs) carrying two, one or no Hmga1 functional alleles using a microarray (miRNA microarray). By this approach, we found a miRNA expression profile that differentiates Hmga1-null MEFs from the wild-type ones. In particular, a significant decrease in miR-196a-2, miR-101b, miR-331 and miR-29a was detected in homozygous Hmga1-knockout MEFs in comparison with wild-type cells. Consistently, these miRNAs are downregulated in most of the analysed tissues of Hmga1-null mice in comparison with the wild-type mice. ChIP assay shows that HMGA1 is able to bind regions upstream of these miRNAs. Moreover, we identified the HMGA2 gene product as a putative target of miR-196a-2, suggesting that HMGA1 proteins are able to downregulate the expression of the other member of the HMGA family through the regulation of the miR-196a-2 expression. Finally, ATXN1 and STC1 gene products have been identified as targets of miR-101b. Therefore, it is reasonable to hypothesize that HMGA1 proteins are involved in several functions by regulating miRNA expression.

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Section: Mir-196a-2 Downregulates Hmga2mentioning

confidence: 99%

Regulation of microRNA expression by HMGA1 proteins

et al. 2009

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“…The HMGIC gene, encoding a nuclear protein with DNA-binding properties, has recently been shown to be the target of translocations in various benign solid tumors Schoenmakers et al, 1995b). The gene is located to 12q15, in the 1.7 megabase`multiple aberration region' (MAR) .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies of benign tumors of mesenchymal origin have detected ectopic transcripts resulting from the fusion of HMGIC and various translocations partners Kazmierczak et al, 1995Kazmierczak et al, , 1996Schoenmakers et al, 1995b). These studies indicate that truncation of HMGIC, in most cases through loss of exon 4 and 5, rather than its fusion to speci®c ectopic coding sequences, is important for its oncogenicity.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the HMGIC gene was localized to this multiple aberration region' (MAR) and reported to be target for translocation in eight di erent benign solid tumor types Schoenmakers et al, 1995b). HMGIC encodes a member of the family of high mobility group (HMG) proteins, characterized by AT-hooks; DNA binding domains that are able to bind to the minor groove of DNA (Reeves and Nissen, 1990).…”

Section: Introductionmentioning

confidence: 99%

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HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas

et al. 1997

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“…Recently, HMGIC was identified to be the target gene affected by these chromosomal aberrations (5,6). HMGIC belongs to a protein family with two other members, HMGI and HMGY, which are produced by alternative splicing from a gene located in chromosome band 6p21 (7).…”

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The Tumor-Associated Gene HMGIC Is Expressed in Normal and Osteoarthritis-Affected Synovia

et al. 2001

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Chromosomal rearrangements involving chromosome bands 12q13-15 are very frequent findings in benign solid tumors, and recently, the primary molecular target for these aberrations was identified as the gene HMGIC. However, mutations in this gene have also been observed in nonneoplastic tissues. In a previous study, we reported breakpoints within HMGIC of synovia affected by osteoarthritis (OA) in two cases with 12q15 aberrations. To analyze further the role of HMGIC in this disease, we have performed cytogenetic, fluorescent in situ hybridization (FISH), RNA, and protein expression analyses on synovial samples from patients with OA and individuals without signs of the disorder. Cytogenetic analysis of short-term cultured cells revealed clonal 12q13-15 aberrations in 2/36 cases of OA synovia and no rearrangement in any of the five controls. With FISH analysis, it was shown that the chromosomal breakpoints in the two aberrant cases were located outside the HMGIC locus. In contrast, at RNA and protein expression analyses, OAaffected as well as normal synovia displayed transcription and translation of the gene. We also analyzed whether immunoreactivity for HMGIC was associated with the proliferation-specific antigen Ki-67, but no correlation between the staining patterns of these proteins was observed. From the results of the present study, it is evident that expression of HMGIC cannot simply be considered a sign of neoplasia or an effect of proliferation.

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Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours

Cited by 522 publications

References 36 publications

Regulation of microRNA expression by HMGA1 proteins

Regulation of microRNA expression by HMGA1 proteins

HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas

The Tumor-Associated Gene HMGIC Is Expressed in Normal and Osteoarthritis-Affected Synovia

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