LOSS OF HETEROZYGOSITY AND REDUCED EXPRESSION OF THE CUTL1 GENE IN UTERINE LEIOMYOMAS

Cytogenetic analyses has revealed deletions and/or rearrangments at se veral chromosomal positions in approximately half of uterine leiomyoma s. The most frequent genetic alteration, deletion of 7q22, was found i n approximately 35% of studied cases with cytogenetic abnormalities (1 28/366=35%), The same chromosomal band was also found to be deleted in a fraction of acute myeloid leukemias and myelodysplastic syndromes, The frequent deletion of 7q22 in some tumors suggest that a tumor supp ressor gene may be located in this region, The human Cut-like homeobox gene, CUTL1, is one of the genes localized to 7q22 and it was shown p reviously to encode a transcriptional repressor that down-modulates th e expression of c-Myc, Activation of the c-Myc oncogenic potential has been shown in many cancers to result from alterations in one or the o ther of its several mechanisms of regulation, These observations led u s to hypothesize that CUTL1 could act as a tumor suppressor gene, In t he present study, we have identified polymorphic markers within and di rectly adjacent to CUTL1 at 7q22 and demonstrated that these markers a re present in a commonly deleted region in seven out of 50 uterine lei omyomas samples examined, Furthermore, Northern blot analysis revealed that CUTL1 mRNA levels were reduced in eight tumors out of 13. These results suggest that CUTL1 may act as a tumor suppressor gene whose in activation could be of pathological importance in the etiology of uter ine leiomyomas.