Gene fusion involving HMGIC is a frequent aberration in uterine leiomyomas.
HMGIC, a high-mobility-group protein gene encoding an architectural transcription factor, was recently identified as the target of gene fusion in a variety of human benign mesenchymal tumors; some of these events were chromosomal translocations involving 12q13-15. HMGIC consists of three DNA-binding domains (encoded by exons 1-3), a spacer, and an acidic carboxyl-terminal regulatory domain (exons 4-5). To determine the spectrum and nature of the aberrations in uterine myomas in Japanese patients, we systematically examined the tumors of 45 patients for all possible types of gene fusions involving HMGIC, by means of 3'-rapid amplification of cDNA ends (RACE) and reverse transcriptase-polymerase chain reaction (RT-PCR) experiments. HMGIC gene fusions were found in 16 (36%) of the tumors; aberrant splicings to five cryptic sequences located in introns of the HMGIC gene were found in 11 of these cases, and translocations causing juxtaposition to other genes, such as COX6C and RA D51B, were found in 5. In all fusion transcripts, the first two or three exons of HMGIC were fused to ectopic sequences. Our results suggest that a fusion event, resulting in the separation of the DNA-binding domains of HMGIC from the spacer and the acidic carboxyl-terminal regulatory domain, is a common tumorigenic mechanism in the development of uterine myomas.
Mine
N
N
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
Kurose
K
K
Nagai
H
H
Doi
D
D
Ota
Y
Y
Yoneyama
K
K
Konishi
H
H
Araki
T
T
Emi
M
M
D017398:Alternative Splicing / Q000235:genetics; D002869:Chromosome Aberrations / Q000235:genetics*; D019457:Chromosome Breakage / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D025743:HMGA2 Protein / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007889:Leiomyoma / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014178:Translocation, Genetic / Q000235:genetics; D014594:Uterine Neoplasms / Q000235:genetics*
D025743:HMGA2 Protein; D012333:RNA, Messenger