Rearrangements of the high mobility group protein family genes and the molecular genetic origin of uterine leiomyomas and endometrial polyps.

The results of cytogenetic studies of uterine leiomyomas have revealed that approximately 50% of these tumours are characterized by clonal chromosomal alterations. These karyotypic deviations are dominated by rearrangements involving a particular part of chromosome 12, i.e. region 12q13-15. We recently showed that the multiple aberration region on chromosome 12q15 harbours recurrent breakpoints frequently found in a variety of benign solid tumours. Within this region a gene encoding for a member of the so called high mobility group family proteins (HMG) was mapped. Further investigation revealed that this gene i.e. HMGI-C is often truncated by the chromosomal aberrations and fused to ectopic DNA sequences leading to fusion genes. Therefore, the results suggest a causal relationship between mutations of the HMGI-C gene and the development of uterine leiomyomas. Apparently identical mutations have been found also in endometrial polyps. Furthermore, there is an obvious coincidence between the chromosomal assignment of other members of the HMG family and the breakpoints of other non-random chromosome abnormalities seen in uterine leiomyomas.