title: Disruption and aberrant expression of HMGA2 as a consequence of diverse chromosomal translocations in myeloid malignancies.
abstract: Chromosomal translocations that target HMGA2 at chromosome band 12q14 are seen in a variety of malignancies, notably lipoma, pleomorphic salivary adenoma and uterine leiomyoma. Although some HMGA2 fusion genes have been reported, several lines of evidence suggest that the critical pathogenic event is the expression of truncated HMGA2 isoforms. We report here the involvement of HMGA2 in six patients with myeloid neoplasia, dysplastic features and translocations or an inversion involving chromosome bands 12q13-15 and either 7p12, 8q22, 11q23, 12p11, 14q31 or 20q11. Breaks within or very close to HMGA2 were found in all six cases by molecular cytogenetic analysis, leading to overexpression of this gene as assessed by RT-PCR. Truncated transcripts consisting of HMGA2 exons 1-2 or exons 1-3 spliced to intron-derived sequences were identified in two patients, but were not seen in controls. These findings suggest that abnormalities of HMGA2 play an important and previously unsuspected role in myelodysplasia.
authors.affiliation: Department of Genetics, School of Science, University of Navarra, Pamplona, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Odero
authors.forename: F H
authors.initials: FH
authors.lastname: Grand
authors.forename: S
authors.initials: S
authors.lastname: Iqbal
authors.forename: F
authors.initials: F
authors.lastname: Ross
authors.forename: J P
authors.initials: JP
authors.lastname: Roman
authors.forename: J L
authors.initials: JL
authors.lastname: Vizmanos
authors.forename: J
authors.initials: J
authors.lastname: Andrieux
authors.forename: J L
authors.initials: JL
authors.lastname: Laï
authors.forename: M J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: N C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D000236:Adenoma / Q000235:genetics; D001483:Base Sequence; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D002897:Chromosomes, Human, Pair 7; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D015321:Gene Rearrangement; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D008067:Lipoma / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D025743:HMGA2 Protein