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Clinical Cancer Research Vol. 5, 2689-2692, October 1999
© 1999 American Association for Cancer Research

Advances in Brief

Detection of Microsatellite Alterations in Plasma DNA of Non-Small Cell Lung Cancer Patients: A Prospect for Early Diagnosis1

Gabriella Sozzi2, Katia Musso, Cathy Ratcliffe, Peter Goldstraw, Marco A. Pierotti and Ugo Pastorino

Division of Experimental Oncology A, Istituto Nazionale Tumori, 20133 Milan, Italy [G. S., K. M., M. A. P.]; Royal Brompton Hospital, London SW3 6NP, United Kingdom [C. R., P. G.]; and Division of Thoracic Surgery, European Institute of Oncology, 20141 Milan, Italy [U. P.]

A major problem in lung cancer is the lack of clinically useful tests for early diagnosis and screening of an asymptomatic population by noninvasive diagnostic procedures. Recent studies have demonstrated the possibility to detect genetic alterations in plasma or serum DNA from patients with various cancers. However, these data rely on small series of aggressive tumors with advanced-stage disease. To determine whether genetic changes in plasma are also detectable in patients with limited disease and thereby potentially useful for early detection, we looked for microsatellite instability (allele shift) and loss of heterozygosity in plasma DNA of 87 stage I-III non-small cell lung cancers and 14 controls. Combining two markers with a high rate of instability (D21S1245) and loss of heterozygosity (FHIT locus), a microsatellite alteration was observed in 49 of 87 (56%) non-small cell lung cancer tumors and in 35 of 87 (40%) plasma samples. Thirty of 49 (61%) of the cases showing tumor alterations also displayed a change in plasma DNA; in addition, 5 patients displayed alterations in plasma samples only. None of the control individuals had genetic changes in plasma. No association was found between the frequency of microsatellite alterations in plasma and tumor stage or histology. Of interest, plasma DNA abnormalities were detectable in 43% of pathological stage I cases and in 45% of tumors up to 2 cm in maximum diameter. These findings highlight new prospects for early tumor detection by noninvasive screening procedures based on the analysis of genetic changes in plasma.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Copyright © 1999 by the American Association for Cancer Research.