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25 Cancer Diagnosis and DNA Replication

Nicholas Coleman, Anthony D. Mills, Ronald A. Laskey


Many of the commonest cancers can be treated more successfully when they are detected early, either as precursor lesions or as early-stage malignancies. The choice of markers for early detection poses a dilemma. The aims are to distinguish cancer cells from normal cells, but to detect all types of cancer cells, irrespective of the oncogenes or tumor suppressor genes that they mis-express. Here, we argue that DNA replication proteins are exceptionally good markers for early detection of many of the common carcinomas and that they can also provide clinically useful prognostic information. This may seem surprising in view of the fact that these proteins are required for the replication of normal as well as cancer cells. However, if cells are recovered from body fluids after they have been exfoliated from the tissue surface, then replication proteins, such as the MCM proteins, can provide decisive clinical information. The reason for this is that MCM proteins are broken down before cells are shed from normal tissues into the body fluids. Therefore, cells shed from normal tissues should not contain MCM proteins, and this prediction is confirmed in practice. In contrast, malignant and premalignant (dysplastic) cells are not programmed to break down MCM proteins before they are lost from the tumor surface.

We have investigated the clinical value of antibodies against DNA replication proteins for detection of malignant and premalignant cells shed into body fluids. We have focused on those epithelia that are the sites of common cancers. MCM proteins are particularly valuable...

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