Microsatellite alterations in serum DNA of head and neck cancer patients
Homaira Nawroz1, Wayne Koch1, Philippe Anker2, Maurice Stroun2
& David Sidransky1, 3
1Department of Otolaryngology — Head and Neck Surgery, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, Maryland 21205-2196
2laboratory of Plant Biochemistry and Physiology, Pavilion des Isotopes, Faculty of Science, University of Geneva, 20 boulevard d'Yvoy, 1211 Geneva 4, Switzerland
3Correspondence should be addressed to D.S.
Microsatellite DNA alterations are an integral part of neoplastic progression and are valuable as clonal markers for the detection of human cancers1−3. Moreover, recent evidence suggests that senescent tumor cells may release DNA into the circulation, which is subsequently carried by and therefore enriched in the serum and plasma4,5. We tested 21 patients with primary head and neck squamous cell carcinoma (HNSCC) by polymerase chain reaction (PCR)−based microsatellite analysis of DNA from lymphocytes and paired serum samples. Patients were scored for alterations as defined by the presence of new alleles (shifts) or loss of heterozygosity (LOH) in serum at each of 12 markers and then compared with primary tumor DNA. Six out of 21 patients (29%) were found to have one or more microsatellite alterations in serum precisely matching those in the primary tumors. All six patients had advanced disease (stage III or IV); five of these patients had nodal metastases, three later developed distant metastases, and four died of disease. Microsatellite analysis of serum represents a novel method for the detection of circulating tumor cell DNA. If these results are confirmed in larger studies, microsatellite markers may be useful in assessing tumor burden in cancer patients.
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