Cancer Research Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine  AACR Conference on Molecular Diagnostics
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
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation

[Cancer Research 54, 1634-1637, April 1, 1994]
© 1994 American Association for Cancer Research

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mao, L.
Right arrow Articles by Sidransky, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mao, L.
Right arrow Articles by Sidransky, D.

Detection of Oncogene Mutations in Sputum Precedes Diagnosis of Lung Cancer1

Li Mao, Ralph H. Hruban, Jay O. Boyle, Melvyn Tockman and David Sidransky2

Departments of Otolaryngology-Head and Neck Surgery [L. M., J. O. B., D. S.] and Environmental Health Sciences [M. T.], Johns Hopkins University; Department of Oncology, Johns Hopkins Oncology Center [D. S.]; and Department of Pathology, Johns Hopkins Hospital [R. H. H.]; Baltimore, Maryland 21205

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.

1 This work was supported by National Cancer Institute Grant 1P50 CA58184-01 and a collaborative research agreement with Oncor, Inc., Gaithersburg, MD.

2 To whom requests for reprints should be addressed, at Johns Hopkins University, School of Medicine, Department of Otolaryngology—Head and Neck Surgery, Head and Neck Cancer Research Division, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2195.

Received 12/28/93. Accepted 2/22/94.




This article has been cited by other articles:


Home page
Clin. Chem.Home page
A. K. Pathak, M. Bhutani, S. Kumar, A. Mohan, and R. Guleria
Circulating Cell-Free DNA in Plasma/Serum of Lung Cancer Patients as a Potential Screening and Prognostic Tool
Clin. Chem., October 1, 2006; 52(10): 1833 - 1842.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
M. A. Jackson, I. Lea, A. Rashid, S. D. Peddada, and J. K. Dunnick
Genetic Alterations in Cancer Knowledge System: Analysis of Gene Mutations in Mouse and Human Liver and Lung Tumors
Toxicol. Sci., April 1, 2006; 90(2): 400 - 418.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
V. Schmiemann, A. Bocking, M. Kazimirek, A. S. C. Onofre, H. E. Gabbert, R. Kappes, C. D. Gerharz, and H. J. Grote
Methylation Assay for the Diagnosis of Lung Cancer on Bronchial Aspirates: A Cohort Study
Clin. Cancer Res., November 1, 2005; 11(21): 7728 - 7734.
[Abstract] [Full Text] [PDF]


Home page
ThoraxHome page
S S Birring and M D Peake
Symptoms and the early diagnosis of lung cancer
Thorax, April 1, 2005; 60(4): 268 - 269.
[Full Text] [PDF]


Home page
CarcinogenesisHome page
P. Keohavong, Q. Lan, W.-M. Gao, K.-C. Zheng, H. H. Mady, M. F. Melhem, and J. L. Mumford
Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan Wei County, China
Carcinogenesis, February 1, 2005; 26(2): 303 - 308.
[Abstract] [Full Text] [PDF]


Home page
Ann. N. Y. Acad. Sci.Home page
T. CARSTENSEN, B. SCHMIDT, E. ENGEL, B. JANDRIG, C. WITT, and M. FLEISCHHACKER
Detection of Cell-Free DNA in Bronchial Lavage Fluid Supernatants of Patients with Lung Cancer
Ann. N.Y. Acad. Sci., June 1, 2004; 1022(1): 202 - 210.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
L. L. Humphrey, S. Teutsch, and M. Johnson
Lung Cancer Screening with Sputum Cytologic Examination, Chest Radiography, and Computed Tomography: An Update for the U.S. Preventive Services Task Force
Ann Intern Med, May 4, 2004; 140(9): 740 - 753.
[Abstract] [Full Text] [PDF]


Home page
CA Cancer J ClinHome page
A. S. Tsao, E. S. Kim, and W. K. Hong
Chemoprevention of Cancer
CA Cancer J Clin, May 1, 2004; 54(3): 150 - 180.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
J. A. Sparano, R. Gray, B. Giantonio, P. O'Dwyer, and R. L. Comis
Evaluating Antiangiogenesis Agents in the Clinic: The Eastern Cooperative Oncology Group Portfolio of Clinical Trials
Clin. Cancer Res., February 15, 2004; 10(4): 1206 - 1211.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
A. McWilliams, J. Mayo, S. MacDonald, J. C. leRiche, B. Palcic, E. Szabo, and S. Lam
Lung Cancer Screening: A Different Paradigm
Am. J. Respir. Crit. Care Med., November 15, 2003; 168(10): 1167 - 1173.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
G. Sozzi, D. Conte, M. Leon, R. Cirincione, L. Roz, C. Ratcliffe, E. Roz, N. Cirenei, M. Bellomi, G. Pelosi, et al.
Quantification of Free Circulating DNA As a Diagnostic Marker in Lung Cancer
J. Clin. Oncol., November 1, 2003; 21(21): 3902 - 3908.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Pathol.Home page
F B J M Thunnissen
Sputum examination for early detection of lung cancer
J. Clin. Pathol., November 1, 2003; 56(11): 805 - 810.
[Abstract] [Full Text] [PDF]


Home page
Genome Res.Home page
A. J. Jeffreys and C. A. May
DNA Enrichment by Allele-Specific Hybridization (DEASH): A Novel Method for Haplotyping and for Detecting Low-Frequency Base Substitutional Variants and Recombinant DNA Molecules
Genome Res., October 1, 2003; 13(10): 2316 - 2324.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
W. Zhu, W. Qin, H. Ehya, J. Lininger, and E. Sauter
Microsatellite Changes in Nipple Aspirate Fluid and Breast Tissue from Women with Breast Carcinoma or Its Precursors
Clin. Cancer Res., August 1, 2003; 9(8): 3029 - 3033.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pathol.Home page
B M Ryan, F Lefort, R McManus, J Daly, P W N Keeling, D G Weir, and D Kelleher
A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up
Mol. Pathol., June 1, 2003; 56(3): 172 - 179.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. Jeanmart, S. Lantuejoul, F. Fievet, D. Moro, N. Sturm, C. Brambilla, and E. Brambilla
Value of Immunohistochemical Markers in Preinvasive Bronchial Lesions in Risk Assessment of Lung Cancer
Clin. Cancer Res., June 1, 2003; 9(6): 2195 - 2203.
[Abstract] [Full Text] [PDF]


Home page
GutHome page
B M Ryan, F Lefort, R McManus, J Daly, P W N Keeling, D G Weir, and D Kelleher
A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up
Gut, January 1, 2003; 52(1): 101 - 108.
[Abstract] [Full Text] [PDF]


Home page
Eur Respir JHome page
C. Brambilla, F. Fievet, M. Jeanmart, F. de Fraipont, S. Lantuejoul, V. Frappat, G. Ferretti, P.Y. Brichon, and D. Moro-Sibilot
Early detection of lung cancer: role of biomarkers
Eur. Respir. J., January 1, 2003; 21(39_suppl): 36S - 44s.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
K. H. Dragnev, D. Stover, and E. Dmitrovsky
Lung Cancer Prevention: The Guidelines
Chest, January 1, 2003; 123(1_suppl): 60S - 71S.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
P. B. Bach, D. E. Niewoehner, and W. C. Black
Screening for Lung Cancer: The Guidelines
Chest, January 1, 2003; 123(1_suppl): 83S - 88S.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
J. M. Silva, J. Silva, A. Sanchez, J. M. Garcia, G. Dominguez, M. Provencio, L. Sanfrutos, E. Jareno, A. Colas, P. Espana, et al.
Tumor DNA in Plasma at Diagnosis of Breast Cancer Patients Is a Valuable Predictor of Disease-free Survival
Clin. Cancer Res., December 1, 2002; 8(12): 3761 - 3766.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
S. G. Spiro and J. C. Porter
Lung Cancer--Where Are We Today?: Current Advances in Staging and Nonsurgical Treatment
Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1166 - 1196.
[Abstract] [Full Text] [PDF]


Home page
ThoraxHome page
G E Goodman
Lung cancer * 1: Prevention of lung cancer
Thorax, November 1, 2002; 57(11): 994 - 999.
[Abstract] [Full Text] [PDF]


Home page
Eur Respir JHome page
J.K. Field and J.H. Youngson
The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection
Eur. Respir. J., August 1, 2002; 20(2): 464 - 479.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
S. A. Belinsky, W. A. Palmisano, F. D. Gilliland, L. A. Crooks, K. K. Divine, S. A. Winters, M. J. Grimes, H. J. Harms, C. S. Tellez, T. M. Smith, et al.
Aberrant Promoter Methylation in Bronchial Epithelium and Sputum from Current and Former Smokers
Cancer Res., April 1, 2002; 62(8): 2370 - 2377.
[Abstract] [Full Text] [PDF]


Home page
Ann. Surg. Oncol.Home page
J. M. Silva, J. M. Garcia, G. Dominguez, J. Silva, C. Miralles, B. Cantos, S. Coca, M. Provencio, P. Espana, and F. Bonilla
Persistence of Tumor DNA in Plasma of Breast Cancer Patients After Mastectomy
Ann. Surg. Oncol., January 1, 2002; 9(1): 71 - 76.
[Abstract] [Full Text] [PDF]


Home page
J. Mol. Diagn.Home page
A. K. El-Naggar, L. Mao, G. Staerkel, M. M. Coombes, S. L. Tucker, M. A. Luna, G. L. Clayman, S. Lippman, and H. Goepfert
Genetic Heterogeneity in Saliva from Patients with Oral Squamous Carcinomas: Implications in Molecular Diagnosis and Screening
J. Mol. Diagn., November 1, 2001; 3(4): 164 - 170.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
F. R. Khuri, J. S. Lee, S. M. Lippman, J. J. Lee, S. Kalapurakal, R. Yu, J. Y. Ro, R. C. Morice, W. K. Hong, and W. N. Hittelman
Modulation of Proliferating Cell Nuclear Antigen in the Bronchial Epithelium of Smokers
Cancer Epidemiol. Biomarkers Prev., April 1, 2001; 10(4): 311 - 318.
[Abstract] [Full Text]


Home page
Clin. Cancer Res.Home page
M. F. Spafford, W. M. Koch, A. L. Reed, J. A. Califano, L. H. Xu, C. F. Eisenberger, L. Yip, P. L. Leong, L. Wu, S. X. Liu, et al.
Detection of Head and Neck Squamous Cell Carcinoma among Exfoliated Oral Mucosal Cells by Microsatellite Analysis
Clin. Cancer Res., March 1, 2001; 7(3): 607 - 612.
[Abstract] [Full Text]


Home page
Cancer Res.Home page
T. Liloglou, P. Maloney, G. Xinarianos, M. Hulbert, M. J. Walshaw, J. R. Gosney, L. Turnbull, and J. K. Field
Cancer-specific Genomic Instability in Bronchial Lavage: A Molecular Tool for Lung Cancer Detection
Cancer Res., February 1, 2001; 61(4): 1624 - 1628.
[Abstract] [Full Text]


Home page
Clin. Cancer Res.Home page
F. R. Hirsch, W. A. Franklin, A. F. Gazdar, and P. A. Bunn Jr.
Early Detection of Lung Cancer: Clinical Perspectives of Recent Advances in Biology and Radiology
Clin. Cancer Res., January 1, 2001; 7(1): 5 - 22.
[Abstract] [Full Text]


Home page
Clin. Chem.Home page
S. J. Clayton, F. M. Scott, J. Walker, K. Callaghan, K. Haque, T. Liloglou, G. Xinarianos, S. Shawcross, P. Ceuppens, J. K. Field, et al.
K-ras Point Mutation Detection in Lung Cancer: Comparison of Two Approaches to Somatic Mutation Detection Using ARMS Allele-specific Amplification
Clin. Chem., December 1, 2000; 46(12): 1929 - 1938.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
W. A. Palmisano, K. K. Divine, G. Saccomanno, F. D. Gilliland, S. B. Baylin, J. G. Herman, and S. A. Belinsky
Predicting Lung Cancer by Detecting Aberrant Promoter Methylation in Sputum
Cancer Res., November 1, 2000; 60(21): 5954 - 5958.
[Abstract] [Full Text]


Home page
JCOHome page
M. Kersting, C. Friedl, A. Kraus, M. Behn, W. Pankow, and M. Schuermann
Differential Frequencies of p16INK4a Promoter Hypermethylation, p53 Mutation, and K-ras Mutation in Exfoliative Material Mark the Development of Lung Cancer in Symptomatic Chronic Smokers
J. Clin. Oncol., September 18, 2000; 18(18): 3221 - 3229.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
G. Ferretti, G. Curigliano, U. Pastorino, A. Cittadini, G. Flamini, M. G. Calabrò, Tommaso De Pas, L. Orlando, M. Mandalà, M. Colleoni, et al.
Detection by Denaturant Gradient Gel Electrophoresis of Tumor-specific Mutations in Biopsies and Relative Bronchoalveolar Lavage Fluid from Resectable Non-Small Cell Lung Cancer
Clin. Cancer Res., June 1, 2000; 6(6): 2393 - 2400.
[Abstract] [Full Text]


Home page
Clin. Chem.Home page
C. J. Fuery, H. L. Impey, N. J. Roberts, T. L. Applegate, R. L. Ward, N. J. Hawkins, C. A. Sheehan, R. O'Grady, and A. V. Todd
Detection of Rare Mutant Alleles by Restriction Endonuclease-mediated Selective-PCR: Assay Design and Optimization
Clin. Chem., May 1, 2000; 46(5): 620 - 624.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
W. N. ROM, J. G. HAY, T. C. LEE, Y. JIANG, and K.-M. TCHOU-WONG
Molecular and Genetic Aspects of Lung Cancer
Am. J. Respir. Crit. Care Med., April 1, 2000; 161(4): 1355 - 1367.
[Full Text]


Home page
ChestHome page
W. A. Franklin
Diagnosis of Lung Cancer : Pathology of Invasive and Preinvasive Neoplasia
Chest, April 1, 2000; 117(4_suppl_1): 80S - 89S.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
G. Sozzi, K. Musso, C. Ratcliffe, P. Goldstraw, M. A. Pierotti, and U. Pastorino
Detection of Microsatellite Alterations in Plasma DNA of Non-Small Cell Lung Cancer Patients: A Prospect for Early Diagnosis
Clin. Cancer Res., October 1, 1999; 5(10): 2689 - 2692.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. Sanchez-Cespedes, M. Esteller, K. Hibi, F. O. Cope, W. H. Westra, S. Piantadosi, J. G. Herman, J. Jen, and D. Sidransky
Molecular Detection of Neoplastic Cells in Lymph Nodes of Metastatic Colorectal Cancer Patients Predicts Recurrence
Clin. Cancer Res., September 1, 1999; 5(9): 2450 - 2454.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
B. Vogelstein and K. W. Kinzler
Digital PCR
PNAS, August 3, 1999; 96(16): 9236 - 9241.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. M. Silva, G. Dominguez, J. M. Garcia, R. Gonzalez, M. J. Villanueva, F. Navarro, M. Provencio, S. San Martin, P. Espana, and F. Bonilla
Presence of Tumor DNA in Plasma of Breast Cancer Patients: Clinicopathological Correlations
Cancer Res., July 1, 1999; 59(13): 3251 - 3256.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. K. Field, T. Liloglou, G. Xinarianos, W. Prime, P. Fielding, M. J. Walshaw, and L. Turnbull
Genetic Alterations in Bronchial Lavage as a Potential Marker for Individuals with a High Risk of Developing Lung Cancer
Cancer Res., June 1, 1999; 59(11): 2690 - 2695.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
Y. Yamaguchi, H. Watanabe, S. Yrdiran, K. Ohtsubo, Y. Motoo, T. Okai, and N. Sawabu
Detection of Mutations of p53 Tumor Suppressor Gene in Pancreatic Juice and Its Application to Diagnosis of Patients with Pancreatic Cancer: Comparison with K-ras Mutation
Clin. Cancer Res., May 1, 1999; 5(5): 1147 - 1153.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
F. Oshita, I. Nomura, K. Yamada, Y. Kato, G. Tanaka, and K. Noda
Detection of K-ras Mutations of Bronchoalveolar Lavage Fluid Cells Aids the Diagnosis of Lung Cancer in Small Pulmonary Lesions
Clin. Cancer Res., March 1, 1999; 5(3): 617 - 620.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
A. F. Gazdar and J. D. Minna
Molecular Detection of Early Lung Cancer
J Natl Cancer Inst, February 17, 1999; 91(4): 299 - 301.
[Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
S. A. Ahrendt, J. T. Chow, L.-H. Xu, S. C. Yang, C. F. Eisenberger, M. Esteller, J. G. Herman, L. Wu, P. A. Decker, J. Jen, et al.
Molecular Detection of Tumor Cells in Bronchoalveolar Lavage Fluid From Patients With Early Stage Lung Cancer
J Natl Cancer Inst, February 17, 1999; 91(4): 332 - 339.
[Abstract] [Full Text] [PDF]


Home page
ThoraxHome page
P J M George
Fluorescence bronchoscopy for the early detection of lung cancer
Thorax, February 1, 1999; 54(2): 180 - 183.
[Full Text]


Home page
ThoraxHome page
M Roland and R M Rudd
Genetics and pulmonary medicine bullet  7: Somatic mutations in the development of lung cancer
Thorax, November 1, 1998; 53(11): 979 - 983.
[Full Text]


Home page
Clin. Chem.Home page
A. F. Gazdar and A. Virmani
Sensitive Methods for the Detection of ras Mutations in Lung Cancer: Some Answers, More Questions
Clin. Chem., July 1, 1998; 44(7): 1376 - 1378.
[Full Text] [PDF]


Home page
Clin. Chem.Home page
V. A. M. C. Somers, D. A. Leimbach, P. H. M. H. Theunissen, J. J. Murtagh Jr., B. Holloway, A. W. Ambergen, and F. B. J. M. Thunnissen
Validation of the Point-EXACCT method in non-small cell lung carcinomas
Clin. Chem., July 1, 1998; 44(7): 1404 - 1409.
[Abstract] [Full Text] [PDF]


Home page
ScienceHome page
D. Sidransky
Nucleic Acid-Based Methods for the Detection of Cancer
Science, November 7, 1997; 278(5340): 1054 - 1058.
[Abstract] [Full Text]


Home page
NEJMHome page
J. A. Brennan, L. Mao, R. H. Hruban, J. O. Boyle, Y. J. Eby, W. M. Koch, S. N. Goodman, and D. Sidransky
Molecular Assessment of Histopathological Staging in Squamous-Cell Carcinoma of the Head and Neck
N. Engl. J. Med., February 16, 1995; 332(7): 429 - 435.
[Abstract] [Full Text] [PDF]


Home page
NEJMHome page
R. H. Hruban, P. van der Riet, Y. S. Erozan, and D. Sidransky
Molecular Biology and the Early Detection of Carcinoma of the Bladder -- The Case of Hubert H. Humphrey
N. Engl. J. Med., May 5, 1994; 330(18): 1276 - 1278.
[Full Text]




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
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 1994 by the American Association for Cancer Research.