Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse

SAMD9 is located on human chromosome 7q21.2 with a paralogous gene sterile alpha motif domain 9 like (SAMD9L) in the head-to-tail orientation. Although both genes are present in a variety of species, the orthologue for SAMD9 is lost in the mouse lineage due to a unique genomic rearrangement. Both SAMD9 and SAMD9L are ubiquitously expressed in human tissues. SAMD9 is expressed at a lower level in a variety of neoplasms associated with β-catenin stabilization, such as aggressive fibromatosis, breast, and colon cancers. SAMD9 and SAMD9L contain an amino-terminal SAM domain, but the remainder of the predicted protein structure does not exhibit substantial homology to other known protein motifs. The putative protein product of SAMD9 localizes to the cytoplasm. In vitro data shows that SAMD9 negatively regulates cell proliferation. Over expression of SAMD9 in the colon cancer cell line, SW480, reduces the volume of tumors formed when transplanted into immune-deficient mice.SAMD9 and SAMD9L are a novel family of genes, which play a role regulating cell proliferation and suppressing the neoplastic phenotype. This is the first report as far as we know about a human gene that exists in rat, but is lost in mouse, due to a mouse specific rearrangement, resulting in the loss of the SAMD9 gene.Neoplasia can be driven by a variety of mechanisms. In many cases, oncogenic mutations result in the dysregulation of transcription. This is the case in mutations resulting in β-catenin stabilization in tumors, as stabilized β-catenin activates transcription factors in the Tcf/Lef family. These transcription factors regulate gene expression in a tissue specific manner [1,2]. Aggressive fibromatosis, also known as desmoid tumor, is a locally invasive soft tissue tumor composed of a clonal proliferation of mesenchymal, fibroblast-like, cells [3]. Somatic mutations in either the Adenomatous Polypisis Coli (APC) or β-catenin genes, resulting in the stabilization of β-catenin protein, are presen