Plasma DNA microsatellite panel as sensitive and tumor-specific marker in lung cancer patients.

Abstract

The majority of lung cancer patients have tumor-derived genetic alterations in circulating plasma DNA that could be exploited as a diagnostic tool. We used fluorescent microsatellite analysis to detect alterations in plasma and tumor DNA in 34 patients who underwent bronchoscopy for lung cancer, including 11 small cell lung cancer (SCLC) and 23 nonsmall cell lung cancer (NSCLC) (12 adenocarcinomas, 11 squamous cell carcinomas) and 20 controls. Allelotyping was performed with a selected panel of 12 microsatellites from 9 chromosomal regions 3p21, 3p24, 5q, 9p, 9q, 13q, 17p, 17q and 20q. Plasma DNA allelic imbalance (AI) was found in 88% (30 of 34 patients), with a similar sensitivity in SCLC and NSCLC. In the 24 paired available tumor tissues, 83% (20 of 24) presented at least 1 AI. Among these patients, 85% (17 of 20) presented also at least 1 AI in paired plasma DNA, but the location of the allelic alterations in paired plasma and tumor DNA could differ, suggesting the presence of heterogeneous tumor clones. None of the 20 controls displayed plasma or bronchial DNA alteration. A reduced panel of six markers (at 3p, 5q, 9p, 9q) showed a sensitivity of 85%. Moreover, a different panel of microsatellites at 3p and 17p13 in SCLC and at 5q, 9p, 9q and 20q in NSCLC patients could be specifically used. Analysis of plasma DNA using this targeted panel could be a valuable noninvasive test and a useful tool to monitor disease progression without assessing the tumor.

• Authors: Michèle Beau-Faller, Marie Pierre Gaub, Anne Schneider, Xavier Ducrocq, Gilbert Massard, Bernard Gasser, Marie Pierre Chenard, Romain Kessler, Philippe Anker, Maurice Stroun, Emmanuel Weitzenblum, Gabrielle Pauli, Jean Marie Wihlm, Elisabeth Quoix, Pierre Oudet
• Journal: International journal of cancer (Int J Cancer) Vol. 105 Issue 3 Pg. 361-70 (Jun 20 2003) ISSN: 0020-7136 [Print] United States
• PMID: 12704670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Biomarkers, Tumor
• DNA

Topics

• Adenocarcinoma (blood, genetics)
• Adult
• Aged
• Aged, 80 and over
• Alleles
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Small Cell (blood, genetics)
• Carcinoma, Squamous Cell (blood, genetics)
• Chromosome Mapping
• DNA (metabolism)
• Disease Progression
• Female
• Genotype
• Humans
• Lung Neoplasms (blood, genetics, mortality)
• Male
• Microsatellite Repeats
• Middle Aged
• Sensitivity and Specificity