Prognostic Significance of Loss-of-Heterozygosity of the CUTL1 Putative Tumor Suppressor Gene in Breast Cancers

摘要

Previous studies suggested that the human Cut gene, CUTL1, could function as a tumor suppressor gene whose deletion and/or mutation may be involved in breast cancer. During this past year, we have determined the complete CUTL1 exon/intron structure. This effort allowed us to determine that three polymorphic markers on 7q22 were located within the boundaries of the CUTL1 gene. As a first step to verify whether LOH of CUTL1 may occur in breast cancer, we used these markers to analyze breast tumor DNA samples from two cohorts of patients that had previously been characterized regarding LOH of 7q31, the chromosomal region adjacent to 7q22 (Bieche et al., 97 (ref. 33); Lin et al., 96 (ref. 34)). We then perform LOH studies using DNA samples from the Manitoba Breast Tumor Bank. Our results revealed 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 the three polymorphic markers that are located within the CUTL1 gene. These genetic data together with other biochemical analyses support the contention that CUTL1 is a candidate tumor suppressor gene.