Gene fusion involving HMGIC is a frequent aberration in uterine leiomyomas

HMGIC, a high-mobility-group protein gene encoding an architectural transcr iption factor, was recently identified as the target of gene fusion in a va riety of human benign mesenchymal tumors; some of these events were chromos omal 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 exami ned the tumors of 45 patients for all possible types of gene fusions involv ing HMGIC, by means of 3 ' -rapid amplification of cDNA ends (RACE) and rev erse transcriptase-polymerase chain reaction (RT-PCR) experiments. HMGIC ge ne 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 II of these cases, and translocations causing juxtaposition to other genes, such as COX6C and RAD51B, 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 regulato ry domain, is a common tumorigenic mechanism in the development of uterine myomas.