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 (C57BL×DBA2) F1 (B6D2F1) females. LOH analysis was performed by polymerase chain reaction amplification 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.