Conventional serum tumor markers are soluble glycoproteins that have proven
clinically useful for the initial diagnosis as well as the follow-up in mu
ltiple tumor entities. However, a number of tumors lack known tumor markers
or the tumor markers are characterized by either low sensitivity or specif
icity. The detection of disseminated tumor cells in the blood by reverse tr
anscriptase polymerase chain reaction (RT-PCR) techniques has offered a bro
adened spectrum of minimally invasive tumor detection. However, these proce
dures are laborious and costly. Recently, microsatellite analysis, a PCR-ba
sed method for detection of tumor-specific DNA alterations, identified tumo
r DNA in the plasma and serum of cancer patients. According to the literatu
re, the specificity of this procedure equals 100% because controls did not
exhibit microsatellite alterations in their plasma or serum DNA. Non-cell-b
ound, free tumor DNA in the plasma or serum can be identified just as well
by detection of other genetic or epigenetic DNA alterations, such as mutati
ons or DNA methylation differences. This article summarizes the current lit
erature on the detection of tumor DNA in the plasma and serum of cancer pat
ients, including own data obtained from patients with clear cell renal carc
inoma. The potential clinical value of such molecular tumor markers for the
initial diagnosis and the follow-up of cancer patients will be discussed.