Significant correlation between the breakpoints of rare clonal aberrationsin benign solid tumors and the assignment of HMGIY retropseudogenes

Recently, we described a mechanism by which a retropseudogene, during evolu tion, becomes an exon of a pre-existing active gene. Similar mechanisms may account for the activation of processed genes by chromosomal rearrangement s in neoplasms. Because genes of the high-mobility group protein family HMG I(Y) are known to be involved in the development of a variety of benign sol id tumors, it was the aim of the present study to analyze break-points of c lonal chromosome abnormalities in that group of benign tumors for a possibl e correlation with retropseudogenes of the HMGIY gene. Whereas the HMGIYL1 retrospeudogene has recently been mapped to Xp22.1, we assigned a further r etropseudogene by FISH to 4q13, and database research allowed us to assign a third retropseudogene to 12q24.1. Sequence analyses of these retropseudog enes revealed high-identity indices to the HMGIY gene and no frame-shift di vergences, Breakpoint information was obtained from cytogenetic aberrations in uterine leiomyomas, lipomas, pleomorphic adenomas, and pulmonary chondr oid hamartomas because, in all of these tumor entities, cytogenetic subgrou ps 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 c an be affected by chromosomal rearrangements in benign human tumors. (C) 20 01 Elsevier Science Inc. All rights reserved.