Loss of heterozygosity on murine chromosome 6 in two-stage carcinogenesis: evidence for a conserved tumor suppressor gene

Abstract

We have recently demonstrated that loss of heterozygosity (LOH) at 7q31 is frequent in many kinds of human primary tumors and that introducing a single human chromosome (hchr) 7 into a murine squamous cell carcinoma (SCC)-derived cell line suppresses the malignant phenotype. To investigate whether the putative tumor suppressor gene on hchr 7 is conserved in mice, we studied LOH on mouse chromosome (mchr) 6 in chemically induced SCCs in (C57BL6DBA2) F1 (B6D2F1) females. LOH analysis was performed by polymerase chain reaction ampli®cation of 17 (CA) n microsatellite repeats in mchr 6 A1-C3. As expected, all the B6D2F1-derived tumors were informative for all the locus assayed. The highest percentage of LOH in the hchr 7q-homologous segment was found at D6Mit50 (60.0%) and the other markers in this segment had LOH incidences normally distributed around the peak. The high incidence of LOH in the tumors studied suggests that a tumor suppressor gene relevant to the development of epithelial cancers is present on mchr 6 A2. As this segment is homologous with hchr 7q31, these data suggest that the putative tumor suppressor gene is conserved in the two species and explains the suppression of tumorigenicity when a single hchr 7 is introduced to a murine SCC cell line.

Identification of a 1300 kilobase deletion unit on chromosome 7q31.3 in invasive epithelial ovarian carcinomas

“…We only observed a 29% LOH (eight of 28 informative cases) rate for D7S522. This was similar to the results of Kerr et al (1996) (34%) but di ers from the results of Zenklusen et al (1995b) who reported 73% LOH detection (14 of 19 informative cases) in D7S522. The discrepancy between our results and those of Zenklusen et al (1995b) may be due to the total number of informative cases and cases of di erent stages and grades that were examined.…”

“…Zenklusen et al (1995b) examined LOH in chromosome 7q in 26 primary ovarian carcinomas using 14 (C-A)n microsatellite repeats. All 26 cases exhibited LOH at one or more loci on 7q with 73% LOH detected in D7S522 at 7q31.1.…”

Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines

“…We have mapped CAVEOLIN-1 to human chromosome 7q31.1, as a candidate for a multi-tissue tumour suppressor gene that has been localized to this subchromosomal region . Like CAVEOLIN-1, this tumour suppressor gene is also conserved in mouse (Zenklusen et al, , 1997. Incidences of LOH of over 80% have been detected in breast carcinomas (Zenklusen et al, 1994a), implying that the chromosome 7-tumour suppressor gene is the most frequently inactivated target during breast Lee et al, 1998).…”

“…Here, we report the mapping of the gene encoding Caveolin-1 to human chromosome 7q31, in proximity to the marker D7S522, which has been mapped to q31.1. A number of studies has revealed a high incidence of loss of heterozygosity (LOH) at 7q31 in a broad range of human tumours, including carcinomas of the breast (Bieche et al, 1992;Zenklusen et al, 1994a), colon (Zenklusen et al, 1995a), kidney (Shridhar et al, 1997), ovary (Kerr et al, 1996;Koike et al, 1997;Zenklusen et al, 1995b), pancreas (Achille et al, 1996), prostate (Takahashi et al, 1995;Zenklusen et al, 1994b), and stomach (Kuniyasu et al, 1994), as well as squamous cell carcinomas of the head and neck (Zenklusen et al, 1995a, Loughran et al, 1997. The highest frequency of LOH was observed at D7S522.…”

Differential loss of heterozygosity at 7q31.2 in follicular and papillary thyroid tumors

“…Recent studies have shown frequent LOH of microsatellite markers on the long arm of chromosome 7, speci®cally at band q31 in several types of tumor including breast (Devilee et al, 1997;Lin et al, 1996;Zenklusen et al, 1994a), ovarian (Koike et al, 1997;Zenklusen et al, 1995a), pancreatic (Achille et al, 1996), prostatic (Oakahashi et al, 1995;Zenklusen et al, 1994b), and squamous cell carcinoma of the head and neck (Zenklusen et al, 1995b). One microsatellite marker, D7S522, has been described as the most frequently deleted marker in many di erent tumor types (Achille et al, 1996;Devilee et al, 1997;Zenklusen et al, 1994a).…”