DCC (deleted in colorectal cancer) inactivation in hematological malignancies.

ABSTRACT

DCC (Deleted in Colorectal Cancer) is a putative tumor suppressor gene located on chromosome band 18q21. Allelic deletions of one DCC locus have been found in more than 70% of colorectal carcinomas. Loss of DCC expression has been detected in 80% of all colorectal cancers and in many other types of tumor. DCC is expressed in normal bone marrow and peripheral lymphocytes, nevertheless DCC expression was absent or greatly reduced in 30% of acute leukemias and in 25% of Chronic Myelogenous Leukemias (CML). DCC encodes a transmembrane glycoprotein closely related to the adhesion molecules of the Neural Cell Adhesion Molecule (N-CAM) family. Glycoproteins of this family function like cell surface receptors and are involved in the regulation of many functions including cell recognition and cell differentiation. Highly specialized adhesion molecules participate in the regulation of hemopoiesis by mediating the interactions of hemopoietic cells with the components of the bone marrow microenvironment. Therefore, loss of DCC, as well as loss or alteration of other adhesion receptors, could contribute to leukemogenesis by impairing the interactions of the hemopoietic cells with the bone marrow microenvironment.