Significant correlation between the breakpoints of rare clonal aberrations in benign solid tumors and the assignment of HMGIY retropseudogenes.

Recently, we described a mechanism by which a retropseudogene, during evolution, becomes an exon of a pre-existing active gene. Similar mechanisms may account for the activation of processed genes by chromosomal rearrangements in neoplasms. Because genes of the high-mobility group protein family HMGI(Y) are known to be involved in the development of a variety of benign solid tumors, it was the aim of the present study to analyze breakpoints of clonal chromosome abnormalities in that group of benign tumors for a possible correlation with retropseudogenes of the HMGIY gene. Whereas the HMGIYL1 retrospeudogene has recently been mapped to Xp22.1, we assigned a further retropseudogene by FISH to 4q13, and database research allowed us to assign a third retropseudogene to 12q24.1. Sequence analyses of these retropseudogenes revealed high-identity indices to the HMGIY gene and no frame-shift divergences. Breakpoint information was obtained from cytogenetic aberrations in uterine leiomyomas, lipomas, pleomorphic adenomas, and pulmonary chondroid hamartomas because, in all of these tumor entities, cytogenetic subgroups involving genes of the HMGI(Y) family exist. Chromosomal bands harboring HMGIY retropseudogenes were affected with a significantly higher frequency than expected under the assumption of purely randomly occurring breakages. These results support our hypothesis that HMGIY-related retropseudogenes can be affected by chromosomal rearrangements in benign human tumors.