| Abstract: | ABSTRACT: BACKGROUND: CADM1 encodes an immunoglobulin superfamily (IGSF) cell adhesion molecule. Inactivation of CADM1, either by promoter hypermethylation or loss of heterozygosity, has been reported in a wide variety of tumor types, thus it has been postulated as a tumor suppressor gene. FINDINGS: We show for the first time that Cadm1 homozygous null mice die significantly faster than wildtype controls due to an increased tumor incidence (p<0.05) of predominantly lymphomas but also some solid tumors. Furthermore, tumor latency is significantly reduced after irradiation (p<0.003), suggesting there are genes that collaborate with loss of Cadm1 in tumorigenesis. To identify these co-operating genetic events, we performed a Sleeping Beauty transposon-mediated insertional mutagenesis screen in Cadm1 mice, and identified several common insertion sites (CIS) found specifically on a Cadm1-null background (not wildtype background). CONCLUSION: We confirm that Cadm1 is indeed a bona fide tumor suppressor gene and provide new insights into genetic partners that co-operate in Cadm1-mediated tumor suppression. |
