Early cancer cell dissemination and late metastatic relapse:: clinical reflections and biological approaches to the dormancy problem in patients

Two clinical entities, unknown-primary cancer and inadvertent transmission of cancer with organ transplants are reviewed and discussed in the context of early and occult tumor cell dissemination. Both entities are taken as chief witnesses for cell dissemination being an early event in tumor progression. The involuntary transmission of tumor by organ grafts directly supports the notion that very few quiescent cells lodging at improbable sites such as kidney or heart suffice to generate de novo metastatic disease in the organ recipient. As to the nature of the cells and their biological and clinical significance a short review is given on the detection of disseminated cells in bone marrow and their prognostic significance for a metastatic relapse in patients with resected primary tumors. A novel single-cell genomic analysis is described, that allows the detection of multiple chromosomal aberration in single tumor cells.