Identification and characterization of novel human transcripts embedded within HMGA2 in t(12;14)(q15;q24.1) uterine leiomyoma

Ingraham, Susan E.; Lynch, Roy A.; Surti, Urvashi; Rutter, Joni L.; Buckler, Alan; Khan, Sohaib A.; Menon, Anil G.; Lepont, Pierig

doi:10.1016/j.mrfmmm.2006.07.007

Cited by 12 publications

(9 citation statements)

References 40 publications

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“…A recent study found alterations in the gene expression profile of ULs. HMGA2, a member of the high-mobility-group gene frequently aberrantly expressed in fibroids, maps at 12q15, a region often rearranged at t (12;14) and commonly observed in ULs (5).…”

Section: Introductionmentioning

confidence: 99%

SPARC-like1 mRNA is overexpressed in human uterine leiomyoma

Mencalha

Levinsphul²,

Deterling³

et al. 2008

Mol Med Report

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Abstract. Uterine leiomyomas (ULs), also known as fibroids, are benign and monoclonal tumors frequently found in the female population. The genetic alterations that contribute to UL tumor development have not been well established, and the goal of this study was to reveal gene expression variation between ULs and healthy uterine tissue. We compared the gene expression profiles of 13 UL tumors with that of their adjacent normal tissue using the Differential Display mRNA assay (DDRT-PCR). Among the genes upregulated in some of the UL samples, several genes previously described in the context of cancer were identified, namely LIMK1, MCM3 and UHRF1. In addition, we identified a cDNA present in UL samples from distinct patients, which was absent from their normal tissue. Direct sequencing of this cDNA revealed a human SPARC-like1 (SPARCL1) mRNA homology. Through semi-quantitative PCR, we demonstrated that SPARCL1 was upregulated in approximately 77% of UL samples, but was absent in normal tissue. Real-time PCR (QPCR) revealed that SPARCL1 expression was increased 5-fold in ULs compared to adjacent normal tissue. These results suggest that the SPARCL1 gene is involved in UL development.

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Section: Introductionmentioning

confidence: 99%

SPARC-like1 mRNA is overexpressed in human uterine leiomyoma

Mencalha

Levinsphul²,

Deterling³

et al. 2008

Mol Med Report

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“…This supports the idea of the implication of HMGA2 in pathogenesis, although its function is not yet well understood in these neoplasms. 4 However, this gene is also a target of chromosomal rearrangements in some benign solid tumors 19,20 such as mesenchymal tumors: [21][22][23][24] in particular, HMGA2 is a prominent feature of conventional lipomas as 75% of these harbor translocation t(3;12) involving it, 3,25,26 but it is also overexpressed or amplified in atypical lipomatous tumor/well-differentiated [27][28][29] and dedifferentiated liposarcomas. Given the involvement of HMGA2 in mesenchymal tumors and particularly adipocytic tumors and the availability of antibodies usable on paraffin-embedded tissues, we evaluated immunohistochemical expression of this gene in a large series of mesenchymal tumors in order to define its value and limitations for histotyping.…”

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confidence: 99%

Value and limitation of immunohistochemical expression of HMGA2 in mesenchymal tumors: about a series of 1052 cases

et al. 2010

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The high mobility group A (HMGA2) gene encodes a protein that alters chromatin structure and regulates the transcription of many genes; it is implicated in both benign and malignant neoplasias, but its rearrangements are a feature of development of several mesenchymal tumors. Given its implication in these tumors and particularly adipocytic tumors, and the availability of antibodies usable on paraffin-embedded tissues, we evaluated the immunohistochemical expression of this gene in a series of 1052 mesenchymal tumors. The objective was to define the value and limitations of HMGA2 immunohistochemical expression for histotyping, and compare with molecular data reported in the literature. We thus analyzed 880 cases on tissue microarray and 182 cases on whole sections (211 adipocytic tumors, 628 sarcomas, 213 benign mesenchymal tumors, and 10 normal adipose tissues). A nuclear immunostaining was detected in 86% of conventional and intramuscular lipomas, in 86% of well-differentiated liposarcomas and in 67% of dedifferentiated liposarcomas, as opposed to 16% of other benign adipose tumors and to 15% of non-well-differentiated liposarcoma/dedifferentiated liposarcoma sarcomas. Among benign mesenchymal tumors and lesions, it was detected in 90% of nodular fasciitis and in 88% of benign fibrous histiocytomas with respective specificities of 85 and 100%, and in 90% of aggressive angiomyxoma, contrary to other vulvovaginal tumor types, which expressed HMGA2 only rarely. The normal adipose tissue was always negative for HMGA2. Although not specific, immunohistochemical detection of the HMGA2 protein is helpful for the distinction of normal adipose tissue from well-differentiated lesions, particularly on biopsy or on re-excision. It is less sensitive than MDM2/CDK4 for dedifferentiated liposarcomas diagnosis, but it appears more specific to distinguish dedifferentiated liposarcomas from other poorly differentiated sarcomas. Finally, and may be more importantly, HMGA2 is useful for the diagnosis of benign fibrous histiocytoma, nodular fasciitis and vulvovaginal benign mesenchymal tumors.

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“…None of these ncRNAs have been proved to be indispensable in embryo implantation. There is also evidence for the existence of some other long ncRNAs in the uterus along with some other organs (68)(69)(70). The detailed expression pattern of these long ncRNAs during embryo implantation is yet to be determined.…”

Section: Discussionmentioning

confidence: 99%