Chromosomal rearrangements leading to abnormal splicing within intron 4 ofHMGIC?

Fusion of the high-mobility group protein gene HMGIC to other genes due to chromosomal rearrangements occurs in a variety of human benign tumors. In c ontrast to genes clearly derived from other chromosomes, some of the ectopi c sequences fused to HMGIC have been assigned to chromosome 12 by CASH (chr omosome assignment using somatic cell hybrids) analyses and thus can be ass umed either to result from alternative splicing or to represent true ectopi c sequences derived from other genes on chromosome 12. In an attempt: to id entify the ectopic sequences fused to this exon, we have sequenced the enti re intron 4. Four of seven ectopic sequences previously described to be fus ed to exon 4 of HMGIC in different tumors were found to be located within i ntron 4 of the gene and thus are due to abnormal splicing. As for a mechani sm explaining this observation, it can be suggested that breakpoints of chr omosomal aberrations not directly disrupting HMGIC may induce small genomic alterations in their vicinity and thus facilitate abnormal splicing. The l atter mechanism may underlie the development of part of the neoplasms chara cterized by 12q14-15 rearrangements. (C) 2001 Wiley-Liss. Inc.