reported no difference in the phenotype of benign tumors developed in transgenic mice expressing either a full-length or a truncated HMGA2 transcript under the control of a differentiated adipocyte-specific promoter. HMGA2 as a Critical Regulator in Cancer Development. In lipomas, the preferential clustering of HMGA2 breakpoints in the third intron results in the replacement of the acidic C-terminal domain by a variety of ectopic sequences. Epub 2014 Jan 3. Zakharov V, Ren B, Ryan C, Cao W. Histopathology. Hydropic leiomyoma (HLM) is a variant of uterine leiomyoma with characteristic features of zonal distributions of edema, increased vascularity, and tumor cells arranged in nodules or cords. The reason may be that HMGA2 promotes epithelial-mesenchymal transition (EMT) and the acquisition of tumor … Site Map 2008 Jan 23; PMID: 18214854, Rabban JT, Dal Cin P, Oliva E. HMGA2 rearrangement in a case of vulvar aggressive angiomyxoma. RNA-sequencing revealed an HMGA2-WIF1 fusion gene in an ER-positive AME lacking HRAS, PIK3CA and AKT1 somatic mutations. Mehine M, Khamaiseh S, Ahvenainen T, Heikkinen T, Äyräväinen A, Pakarinen P, Härkki P, Pasanen A, Bützow R, Vahteristo P. Cancers (Basel). Ectopic expression of HMGA2 in epithelial cells induces epithelial–mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. We describe a case of a 44-year-old woman with locally advanced aggressive angiomyxoma with a novel translocation high-mobility group AT-hook 2-yes-associated protein 1 (HMGA2-YAP1) fusion, implying … HMGA2 expression was identified in 19 PAs (33.9%) and nine CA ex‐PAs (24.3%). Epub 2017 Oct 20. 107 talking about this. 2003 Nov 1;63(21):7423-7. Bertsch E, Qiang W, Zhang Q, Espona-Fiedler M, Druschitz S, Liu Y, Mittal K, Kong B, Kurita T, Wei JJ. 94 talking about this. 2008 Sep 30. Thank you for joining our Facebook page. Epub 2018 Jul 13. Pathology Outlines Job Search. In contrast, the dysregulation of HMGA2 might cause a malignant phenotype when coupled with MDM2 amplification, as suggested by a study showing that the expression of MDM2 or CDK4 allowed human diploid fibroblast to by-pass HMGA2-induced proliferation arrest. have demonstrated the amplification of exons 1-2 of HMGA2 in all the 38 WDLPS/DDLPS cases studied, against the nonconsistent amplification of exons 3-5. Contact | PMID: 14612541, Quade BJ, Weremowicz S, Neskey DM, Vanni R, Ladd C, Dal Cin P, Morton CC. Inflammatory myofibroblastic tumor with HMGIC rearrangement. Am J Surg Pathol. Epub 2013 Sep 29. Expression was strong and diffuse throughout all PAs, and in four of nine positive CA ex‐PAs. The Pathology Atlas contains mRNA and protein expression data from 17 different forms of human cancer, as well as correlation analysis of mRNA expression and patient survival. Setting: Pedeutour et al. PMID: 20551826, HMGA2: A Potential Biomarker Complement to P53 for Detection of Early-stage High-grade Papillary Serous Carcinoma in Fallopian Tubes. HMGA2 overexpression upregulated IGF2BP2 and pAKT, and silencing the IGF2BP2 gene reduced pAKT levels and reduced HUVEC migration. HMGA2 expression is a highly specific (96.2%), but low-sensitivity (29.8%), marker for PA and CA ex-PA when compared with histological mimics, and is frequently associated with rearrangement of the HMGA2 … 2014 Sep;102(3):621-9. doi: 10.1016/j.fertnstert.2014.06.050. In addition, extragenic breakpoints located 5 or 3 to HMGA2 similar to the rearrangements observed in uterine leiomyomas also occur in lipomas. HMGA2 immunostaining is an affordable and straightforward technique for accurate description of biopsies containing adipose cells. 2014 Aug;27(8):1144-53. doi: 10.1038/modpathol.2013.243. In addition, HMGA2 overexpression could also result from the disruption of the 3UTR causing the loss of function of let-7, a microRNA specifically involved in the posttranscriptional repression of HMGA2. MICROTUBULE-ASSOCIATED PROTEIN 2, abbreviated MAP2, is a common immunostain used in neuropathology and pulmonary pathology. Twenty-five percent (8/32) of leiomyosarcomas had HMGA2 overexpression, and no MED12 mutations were found in HMGA2 positive leiomyosarcoma. Overexpression of HMGA2 in MM and LM cell lines resulted in increased secretion of angiogenesis-associated factors. The staining intensity of HMGA1 and HMGA2 is also significantly higher in adenocarcinomas than in adenomas or reactive atypias. PMID: 14614053, Pentimalli F, Dentice M, Fedele M, Pierantoni GM, Cito L, Pallante P, Santoro M, Viglietto G, Dal Cin P, Fusco A. Suppression of HMGA2 protein synthesis could be a tool for the therapy of well differentiated liposarcomas overexpressing HMGA2. 2006 Oct;25(4):403-7. Douglas B. Flieder, in Pulmonary Pathology (Second Edition), 2018. See : HMGs / HMGAs. Mod Pathol. The protein expression data is derived from antibody-based protein profiling using … Thank you for joining our Facebook page. bisruption and aberrant expression of HMGA2 by chromosomal translocations in myeloid malignancies (15618963), constitutional rearrangement of HMGA2 in a phenotype including extreme somatic overgrowth, advanced endochondral bone and dental ages, a cerebellar tumor, and multiple lipomas (15593017), HMGA2 rearrangements in salivary gland tumors, pleomorphic adenoma of the parotid gland (18828159), uterine leiomyomas (4)Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA. Galindo LJ, Hernández-Beeftink T, Salas A, Jung Y, Reyes R, de Oca FM, Hernández M, Almeida TA. Although CDK4 certainly plays an important role in a majority of cases, our results favor MDM2-HMGA2 instead of MDM2-CDK4 as the crucial couple of genes in WDLPS/DDLPS pathogenesis. HMGA2-LM have a high vasculature density, which likely contributes to tumor growth and disease burden of this leiomyoma subtype. HM G proteins (HMGs) function as architectural factors and are … The expression of HMGA2 in adult tissues is commonly associated with both malignant and benign tumor formation, as well as certain characteristic cancer-promoting mutations.  salivary gland pleomorphic adenoma PMID: 15036898, Dahlen A, Mertens F, Rydholm A, Brosjo O, Wejde J, Mandahl N, Panagopoulos I. Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas. 2010 Jul;34(7):1037-42. Thank you for joining our Facebook page. This protein contains structural DNA-binding domains and may act as a transcriptional regulating factor. HMGA2 and high-grade serous ovarian carcinoma. As an oncofetal protein, HMGA2 plays an important role in development and contributes to the tumorigenesis of many epithelial and mesenchymal tumors. Unable to load your collection due to an error, Unable to load your delegates due to an error. Jin L, Lloyd RV, Nassar A, Lappinga PJ, Sebo TJ, Swartz K, Seys AR, Erickson-Johnson MR, Roth CW, Evers BR, Oliveira AM, Zhang J. Diagn Mol Pathol. 2008 Aug 29. Specifically, HMGA2-LM exhibited increased expression of VEGFA, EGF, bFGF, TGFα, VEGFR1, and VEGFR2 compared to MED12-LM and myometrium. CALIFORNIA, LOS ANGELES (USA). Please enable it to take advantage of the complete set of features! P01 HD057877/HD/NICHD NIH HHS/United States, NCI CPTC Antibody Characterization Program. Results: This website is intended for pathologists and laboratory personnel but not for patients. Thank you for joining our Facebook page. 2002 May;440(5):485-90. 3'RNA Sequencing Accurately Classifies Formalin-Fixed Paraffin-Embedded Uterine Leiomyomas. 2011 Jun;20(2):71-80. However, cooperation between HMGA2 and CDK4, when amplified, may also play an important role. PMID: 12021922, Berner JM, Meza-Zepeda LA, Kools PF, Forus A, Schoenmakers EF, Van de Ven WJ, Fodstad O, Myklebost O. HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas. Some results identifying variability in the dysregulation pattern of HMGA2 in WDLPS/DDLPS, strongly suggest that a misexpression of HMGA2, whatever the mechanism, might be sufficient for tumorigenesis. MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. PMID: 12649198, Van Dorpe J, Dal Cin P, Weremowicz S, Van Leuven F, de Wever I, Van den Berghe H, Fletcher CD, Sciot R. Translocation of the HMGI-C ( HMGA2) gene in a benign mesenchymoma (chondrolipoangioma). PMID: 9205100, Kazmierczak B, Dal Cin P, Sciot R, Van den Berghe H, Bullerdiek J. When positive, a diagnosis of benign adipose lesion can be made with confidence since well-differentiated liposarcomas have never been described in the tracheobronchial tree. Furthermore, all morphologic mimics of PA were negative for PLAG1 or HMGA2. Wu J(1), Wei JJ. PMID: 21532495, HMGA2 is a sensitive but not specific immunohistochemical marker of vulvovaginal aggressive angiomyxoma. Virchows Arch. Oncogene. 2021 Feb 13;12(2):269. doi: 10.3390/genes12020269. (18843278), HMGA2 was identified as one of target genes of the let-7 family of miRNAs and has been found to be suppressed by let-7 in vitro. Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15. Stains & molecular markers - HGAL. 30100 Telegraph Road, Suite 408, Bingham Farms, Michigan 48025 (USA) Rearrangement and overexpression of HMGA2 are observed in lipomas and in other benign tumors such as uterine leiomyomas and salivary gland pleomorphic adenomas. Cancer Res. PMID: 10686944, 1996 - 2021 Humpath.com - Human pathology PMID: 19898227, Hristov AC, Cope L, Reyes MD, Singh M, Iacobuzio-Donahue C, Maitra A, Resar LM. The degradation of p53 is mediated by murine double minute 2 (MDM2) in a proteasome‐dependent manner. These findings strongly suggest that MED12 mutations and HMGA2 overexpression are independent genetic events that occur in leiomyomas, and they may act differently in the tumorigenesis of uterine leiomyomas. RSS 2.0, aggressive angiomyxoma of the lower genital tract (33%) (, HMGA2-associated inflammatory myofibroblastic tumor (IMT) (, HMGA2/RDC1 fusion protein expression in lipomas as the result of chromosome aberrations involving 2q35-37 and 12q13-15. (Fusion of RDC1 with HMGA2 in lipomas). Aim Phyllodes tumours (PTs) categorised as benign, borderline and malignant, account for 1% of all breast tumours. The observation that the tumors developed in HMGA2 transgenic mice were always benign raises the question of the role of HMGA2 in malignancy. Mod Pathol. HMGA1 and HMGA2 might serve to discriminate between reactive atypia, adenoma and adenocarcinoma in ampulla and. Objective: HMGA2 is positive in 14% of reactive atypias, 42% of adenomas, and 86% of adenocarcinomas. HMGA2 gene encodes a protein that belongs to the non-histone chromosomal high mobility group (HMG) protein family (HMGs). Thank you for joining our Facebook page. PMID: 16990720, Dal Cin P, Thomas A, Weremowicz S. An intragenic rearrangement of HMGA2 is not necessary for lipoma formation. 8600 Rockville Pike Subtype-Specific Tumor-Associated Fibroblasts Contribute to the Pathogenesis of Uterine Leiomyoma. Genes Chromosomes Cancer.  lipomas, HMGA2 is a sensitive but not specific immunohistochemical marker of vulvovaginal aggressive angiomyxoma. Of all 178 leiomyomas examined, 74.7%(133/178) of uterine leiomyomas had MED12 mutations. Author information: (1)Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. National Library of Medicine The main outcome measures include vessel density in leiomyomas with HMGA2 (HMGA2-LM) or MED12 (MED12-LM) alteration; angiogenic factor expression in primary leiomyoma and in vitro cell line model; and vessel formation in leiomyoma cells with HMGA2 overexpression in vitro and in vivo. Amplification of 5′-UTR and exons 1–3 (P=0.08) and 3′-UTR (P=0.01) of HMGA2 were associated with longer recurrence-free survival. To study the role of HMGA2 in promoting angiogenesis in uterine leiomyoma (LM). The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy. Genomics of uterine leiomyomas: insights from high-throughput sequencing. Mod Pathol. Epithelial–mesenchymal transition (EMT) is an important process during embryogenesis. High expression of high mobility group protein A2 (HMGA2) is correlated with the invasiveness of gastric cancer and is an independent prognostic factor. Int J Cancer. Published by Elsevier Inc. All rights reserved. HMGA2 and MED12 alterations frequently co-occur in uterine leiomyomas. 572 talking about this. Histological assessment does not always predict tumour behaviour, hindering determination of the clinical course and management. Moreover, some tumors with 12q rearrangements retain the full coding region of HMGA2, suggesting a nondependence of the HMGA2 oncogenic potential on the nature of the transcript. Wu X, Serna VA, Thomas J, Qiang W, Blumenfeld ML, Kurita T. Cancer Res. 2009 Oct 28. HMG proteins (HMGs) function as architectural factors and are essential components of the enhancesome. Clipboard, Search History, and several other advanced features are temporarily unavailable. Thank you for joining our Facebook page. 2003 Mar 15;63(6):1351-8. Design: HMGA2 gene encodes a protein that belongs to the non-histone chromosomal high mobility group (HMG) protein family (HMGs). PLAG1 and HMGA2 rearrangements are the most common genetic events in CA ex-PA regardless of the histologic subtype. Careers. Int J Gynecol Pathol. 103 talking about this. PMID: 18843278, Persson F, Andrén Y, Winnes M, Wedell B, Nordkvist A, Gudnadottir G, Dahlenfors R, Sjögren H, Mark J, Stenman G. High-resolution genomic profiling of adenomas and carcinomas of the salivary glands reveals amplification, rearrangement, and fusion of HMGA2. (23530587), Diagnostic value of HMGAs, p53 and β-catenin in discriminating adenocarcinoma from adenoma or reactive atypia in ampulla and common bile duct biopsies. 1999 Jul 15;112(2):156-60. Thank you for joining our Facebook page. In five CA ex‐PAs, HMGA2 showed weak‐to‐strong multifocal staining within the carcinomatous component, and strong diffuse HMGA2 expression in the residual PA. Secreted factors promoted human umbilical vein endothelial cell (HUVEC) migration, tube formation, and wound healing. 2003 Nov;16(11):1132-40. 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. HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma. Mehine M, Mäkinen N, Heinonen HR, Aaltonen LA, Vahteristo P. Fertil Steril. McCluggage WG, Connolly L, McBride HA. 2004 Mar;149(2):178-9. Cancer Res. Interventions: University research laboratory. Homologous proteins with highly conserved sequences are found in other mammalian species, including lab mice ( … Pathology 49, 215–227 (2017). High mobility group A2 (HMGA2) is an architectural transcription factor that promotes human colorectal cancer (CRC) aggressiveness by modulating the transcription of target genes. Here, we demonstrate that HMGA2 can be … 2013 Apr;62(5):778-87. doi : 10.1111/his.12084 PMID: 23530587, HMGA2 expression analysis in cytological and paraffin-embedded tissue specimens of thyroid tumors by relative quantitative RT-PCR. Bethesda, MD 20894, Copyright (20551826), HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma. However, the mechanism of HMGA2 regulation remains largely uncharacterized. HMGA2 (high mobility group AT-hook 2) HMGA2, the High Mobility Group A2 gene, is a non-histone and architectural transcription factor. PathologyOutlines.com, free, updated outline surgical pathology clinical pathology pathologist jobs, conferences, fellowships, books Ancillary Studies Cytogenetics. MIM.600698 12q14-q15 HGNC:5009 Entrez:8091, Definition: The high mobility group A2 (HMGA2) protein is an architectural transcription factor that has recently been implicated in the development and progression of malignant tumors. Cancer Genet Cytogenet. PLAG1 or HMGA2 rearrangements were identified in 6 (67%) of 9 hypocellular myxoid PAs and in 2 (29%) of 7 cellular PAs. PMID: 18828159, Italiano A, Bianchini L, Keslair F, Bonnafous S, Cardot-Leccia N, Coindre JM, Dumollard JM, Hofman P, Leroux A, Mainguené C, Peyrottes I, Ranchere-Vince D, Terrier P, Tran A, Gual P, Pedeutour F. HMGA2 is the partner of MDM2 in well-differentiated and dedifferentiated liposarcomas whereas CDK4 belongs to a distinct inconsistent amplicon. Some reports based on small series have shown the amplification and overexpression of HMGA2 in a subset of WDLPS/DDLPS. Diagnostic difficulty and patient management are further complicated by a lack of studies and unknown cause of … Hum Reprod Update. It's expression is associated with neuronal, glial or neuroendocrine differentiation. University of Southern California and Children’s Hospital Los Angeles are seeking an M.D., M.D. 164 talking about this. Gynecol Oncol. Accessibility HMGA2, the High Mobility Group A2 gene, plays a very important role in fetal development and carcinogenesis. HMGA2 plays an important role in angiogenesis and the involvement of IGF2BP2-mediated pAKT activity in angiogenesis, which provides a potential novel target for therapy for this subtype of LM. Among them, 93.9%(125/133) of mutations were confined to … | Log in | COVID-19 is an emerging, rapidly evolving situation. / Ph.D. or Ph.D. (or equivalent) Assistant / Associate Professor of Clinical Pathology.Training in pathology, infectious diseases or medical Microbiology with experience in Molecular and clinical microbiology is required. Epub 2014 Aug 5. Main outcome measures: Some authors have proposed that the truncation of HMGA2 followed or not by the addition of ectopic sequences might be the critical steps in HMGA2 oncogenicity. The non-histone chromatin-binding protein HMGA2 is expressed predominantly in the mesenchyme before its differentiation, but it is also expressed in tumors of epithelial origin.

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