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In breast cancer, loss of heterozygosity (LOH) has been described on the long arm of chromosome 7, at band q31, suggesting the presence of a tumor suppressor gene in this region. In this study, we have identified a second region of LOH on 7q, at band 7q22. Deletion of genetic material at 7q22 was found in all tumor types and grades and was associated with increased tumor size. The region of LOH at 7q22 in every case included one or more of three polymorphic markers that are located within the CUTL1 gene. LOH of 7q22 has also been documented in the case of human uterine leiomyomas (Zeng et al., 1997; Ishwad et al., 1997). Interestingly, in both leiomyomas and mammary tumors induced in transgenic mice expressing the Polyomavirus (PyV) large T (LT) antigen, immunocomplexes of CUTL1 and PyV LT antigen were detected (Webster et al., 1998). Altogether, genetic data in human breast cancer and biochemical analyses in breast tumors from transgenic mice suggest that CUTL1 is a candidate tumor suppressor gene. [ABSTRACT FROM AUTHOR]

Cytogenetic analyses has revealed deletions and/or rearrangments at several chromosomal positions in approximately half of uterine leiomyomas. The most frequent genetic alteration, deletion of 7q22, was found in approximately 35% of studied cases with cytogenetic abnormalities (128/366=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 suppressor 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 previously to encode a transcriptional repressor that down-modulates the 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 other of its several mechanisms of regulation. These observations led us to hypothesize that CUTL1 could act as a tumor suppressor gene. In the present study, we have identified polymorphic markers within and directly adjacent to CUTL1 at 7q22 and demonstrated that these markers are present in a commonly deleted region in seven out of 50 uterine leiomyomas 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 inactivation could be of pathological importance in the etiology of uterine leiomyomas. [ABSTRACT FROM AUTHOR]