title: Detection of oncogene mutations in sputum precedes diagnosis of lung cancer.
abstract: The Johns Hopkins Lung Project developed an archive of sputum specimens during a randomized trial of lung cancer screening (1974-1982). We identified 15 patients from that trial who later developed adenocarcinoma of the lung. The primary lung carcinomas from 10 of these 15 patients contained either a ras or a p53 gene mutation. Using a polymerase chain reaction-based assay, stored sputum samples obtained prior to clinical diagnosis were examined for the presence of these same oncogene mutations. In 8 of 10 patients, the identical mutation identified in the primary tumor was also detected in at least one sputum sample. The earliest detection of a clonal population of cancer cells in sputum was in a sample obtained more than 1 year prior to clinical diagnosis. These results provide the basis of a novel approach for detection of lung cancer based on the evolving molecular genetics of this disease.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland 21205.
authors.forename: L
authors.initials: L
authors.lastname: Mao
authors.forename: R H
authors.initials: RH
authors.lastname: Hruban
authors.forename: J O
authors.initials: JO
authors.lastname: Boyle
authors.forename: M
authors.initials: M
authors.lastname: Tockman
authors.forename: D
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000302:isolation & purification; D017931:DNA Primers; D015246:Deoxyribonuclease EcoRI; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D013183:Sputum / Q000166:cytology*
chemical_list: D017931:DNA Primers; D004247:DNA; D015246:Deoxyribonuclease EcoRI