Refined mapping of the region of loss of heterozygosity on the long arm of chromosome 7 in human breast cancer defines the location of a second tumor suppressor gene at 7q22 in the region of the CUTL1 gene

Abstract

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 identi®ed 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.

Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas

“…Nuclear extracts from selected samples of pairs of uterine leiomyomas and matched normal myometrium were prepared as described in Material and Methods and analyzed by EMSA with oligonucleotides containing a CDP/Cut consensus-binding site (CGATATCGAT). DNA and proteins were incubated either with no antibody (lanes 1-10) or with the indicated antibodies (lanes [11][12][13][14]. The diagram shows a schematic representation of the CDP/Cux proteins with their conserved domains and the regions recognized by the respective antibodies.…”

“…9 LOH of CUTL1 was also reported in 12/66 sporadic breast cancers. 11 Altogether these results raised the possibility that CUTL1 may be the tumor-suppressor gene on 7q22. However, this notion contradicts results of DNA binding studies in tissue culture systems.…”

CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers

“…CUX1 is located at chromosome 7q22.1, a region that sustains frequent LOH in several cancers, notably in 14% of uterine leiomyomas 44,45 , 18% of breast cancers 46 , 15-25% of acute myeloid leukaemias (AMLs) and MPDs 47 , and in up to 40% of therapy-associated MPD and AML 48 . Although early cytogenetic studies and polymorphic marker analyses clearly pointed to the presence of a tumour suppressor gene on 7q22.1, the implicated gene was not rapidly identified.…”

Lymphoid apoptosis and myeloid hyperplasia in CCAAT displacement protein mutant mice

“…It is interesting to note that human CDP is located on chromosome 7q22, a region that is often deleted in 7q-related acute myeloid leukemia and myeloid dysplasia. [39][40][41][42][43] In addition, loss of CDP is found in breast tumors 44 and uterine leiomyomas. 45,46 These studies suggest that CDP is a tumor suppressor and that its loss is a significant event in the generation or progression (or both) of myeloid disorders.…”