Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.
Mol Cancer. 2012 May 3;11:29. doi: 10.1186/1476-4598-11-29.
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.
We show for the first time that Cadm1 homozygous null mice die significantly faster than wildtype controls due to the spontaneous development of tumors at an earlier age and an increased tumor incidence of predominantly lymphomas, but also some solid tumors. Tumorigenesis was accelerated after irradiation of Cadm1 mice, with the reduced latency in tumor formation 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 (and not wildtype background).
We confirm that Cadm1 is indeed a bona fide tumor suppressor gene and provide new insights into genetic partners that co-operate in tumorigenesis when Cadm1-expression is lost.
CADM1 编码免疫球蛋白超家族（IGSF）细胞黏附分子。已报道 CADM1 的失活（通过启动子超甲基化或杂合性丢失）存在于多种肿瘤类型中，因此它被假定为一种肿瘤抑制基因。
我们首次表明，由于肿瘤在更早的年龄自发发展且淋巴瘤的发生率增加，Cadm1 纯合子缺失小鼠的死亡率明显高于野生型对照。肿瘤发生在 Cadm1 小鼠照射后加速，肿瘤形成的潜伏期缩短表明存在与 Cadm1 缺失协同作用的基因在肿瘤发生中。为了鉴定这些协同遗传事件，我们在 Cadm1 小鼠中进行了 Sleeping Beauty 转座子介导的插入突变筛选，并在 Cadm1 缺失背景（而非野生型背景）上发现了几个常见的插入位点（CIS）。
我们证实 Cadm1 确实是一种真正的肿瘤抑制基因，并为当 Cadm1 表达缺失时协同促进肿瘤发生的遗传伙伴提供了新的见解。
