Research

Expression levels of HMGA2 in adipocytic tumors correlate with morphologic and cytogenetic subgroups

Hammurabi Bartuma¹ , Ioannis Panagopoulos¹ , Anna Collin¹ , Domenico Trombetta^1,2 , Henryk A Domanski³ , Nils Mandahl¹ and Fredrik Mertens¹

¹  Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

²  Department of Genetics and Microbiology, University of Bari, Bari, Italy

³  Department of Cytology and Pathology, Lund University Hospital, Lund, Sweden

author email corresponding author email

Molecular Cancer 2009, 8:36doi:10.1186/1476-4598-8-36

Published:	9 June 2009

Abstract

Background

The HMGA2 gene encodes a protein that alters chromatin structure. Deregulation, typically through chromosomal rearrangements, of HMGA2 has an important role in the development of several mesenchymal neoplasms. These rearrangements result in the expression of a truncated protein lacking the acidic C-terminus, a fusion protein consisting of the AT-hook domains encoded by exons 1–3 and parts from another gene, or a full-length protein; loss of binding sites for regulatory microRNA molecules from the 3' untranslated region (UTR) of HMGA2 has been suggested to be a common denominator.

Methods

Seventy adipocytic tumors, representing different morphologic and cytogenetic subgroups, were analyzed by qRT-PCR to study the expression status of HMGA2; 18 of these tumors were further examined by PCR to search for mutations or deletions in the 3'UTR.

Results

Type (full-length or truncated) and level of expression varied with morphology and karyotype, with the highest levels in atypical lipomatous tumors and lipomas with rearrangements of 12q13-15 and the lowest in lipomas with 6p- or 13q-rearrangements, hibernomas, spindle cell lipomas and myxoid liposarcomas. All 18 examined tumors showed reduced or absent expression of the entire, or parts of, the 3'UTR, which was not due to mutations at the DNA level.

Conclusion

In adipocytic tumors with deregulated HMGA2 expression, the 3'UTR is consistently lost, either due to physical disruption of HMGA2 or a shift to production of shorter 3'UTR.