A strategy to identify genes associated with circulating solid tumor cell survival in peripheral blood

Efforts in metastasis research have centered on the phenotypic and genetic differences between primary site and metastatic site tumors. However, genes that may be used as molecular markers of metastasis in circulating tumor c ells remain unidentified. Genes regulating the dissemination and survival o f solid tumor cells in the blood, as well as their adaptation to new enviro nments, could be candidates for unique metastatic tumor markers. Differenti al display (DD) was conducted to compare the blood of tumor-free individual s with the blood of patients with lung, breast, and colon cancers. Twenty-o ne up-expressed genes in the tumor patient blood samples but none in the tu mor-free donor blood samples were identified. Nine of these samples were is olated, amplified, and directly sequenced. A gene AB-1 homologous to a Bcl- 2 family member, which might: function as an apoptosis inhibitor, was ident ified. The overexpression of an apoptosis inhibitor in blood from patients with metastatic tumors might be correlated with the capability of solid tum or cells to survive in peripheral blood. This is the first demonstration of the usefulness of comparing control and patient blood samples by DD to fin d novel potential genetic markers identifying metastasis in the blood.