title: Detecting lung cancer in plasma with the use of multiple genetic markers.
abstract: Recent studies have demonstrated the possibility to detect genetic changes in plasma DNA of cancer patients. The goal of this study was to validate a panel of molecular markers for lung cancer detection in plasma DNA. Three markers, p53, FHIT and microsatellite alterations at loci on chromosome 3, were used to detect mutations in tumor and plasma DNA of 64 stage I-III non small cell lung cancer patients. p53 mutations were studied by direct sequencing of exons 5 through 8 in tumor DNA and by plaque hybridization assay and sequencing in plasma DNA. Allelic losses were evaluated by fluorescent PCR in tumor and plasma DNA. p53 genomic mutations were detected in 26 (40.6%) of 64 tumor DNA samples and the identical mutation was identified in plasma of 19 (73.1%) of them. Microsatellite alterations at FHIT and 3p loci were observed in 40 (62.5%) tumors and in 23 (35.9%) plasma samples. Of the 40 patients showing microsatellite alterations in tumors, 19 (47.5%) displayed the same change in plasma DNA. At least 1 of the 3 genetic markers (p53, FHIT and 3p) was altered in plasma of 51.6% of all patients and 60.7% of stage I patients. Moreover, genetic markers in plasma identified 29 of 45 (64.4%) of all stages and 15 of 22 (68.2%) of stage I patients whose tumors had an alteration. These results provide the proof of principle that plasma DNA alterations are tumor-specific in most cases and support blood testing as a noninvasive strategy for early detection.
authors: Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy. francesca.andriani@istitutotumori.mi.it
authors: Francesca
authors: F
authors: Andriani
authors: Davide
authors: D
authors: Conte
authors: Tiziana
authors: T
authors: Mastrangelo
authors: MariaElena
authors: M
authors: Leon
authors: Cathy
authors: C
authors: Ratcliffe
authors: Luca
authors: L
authors: Roz
authors: Giuseppe
authors: G
authors: Pelosi
authors: Peter
authors: P
authors: Goldstraw
authors: Gabriella
authors: G
authors: Sozzi
authors: Ugo
authors: U
authors: Pastorino
mesh_terms: D017766:Acid Anhydride Hydrolases; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D002893:Chromosomes, Human, Pair 3; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D004273:DNA, Neoplasm; D005819:Genetic Markers; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase