Quantification of Free Circulating DNA As a Diagnostic Marker in Lung Cancer

Purpose: Analysis of circulating DNA in plasma can provide a useful marker for earlier lung cancer detection. This study was designed to assess the sensitivity and specificity of a quantitative molecular assay of circulating DNA to identify patients with lung cancer and monitor their disease. Materials and Methods: The amount of plasma DNA was determined through the use of real-time quantitative polymerase chain reaction (PCR) amplification of the human telomerase reverse transcriptase gene (hTERT) in 100 non–small-cell lung cancer patients and 100 age-, sex-, and smoking-matched controls. Screening performance of the assay was calculated through the receiver operating characteristic (ROC) curve. Odds ratios were calculated using conditional logistic regression analysis. Results: Median concentration of circulating plasma DNA in patients was almost eight times the value detected incontrols (24.3 v 3.1 ng/mL). The area under the ROC curve was 0.94 (95% CI, 0.907 to 0.973). Plasma DNA was a strong risk fact...

[1]  Lori J Sokoll,et al.  Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer. , 2003, Journal of the National Cancer Institute.

[2]  U. Pastorino,et al.  p63 immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas? , 2002, The Journal of pathology.

[3]  Li Mao,et al.  hTERT expression is a prognostic factor of survival in patients with stage I non-small cell lung cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[4]  D. Sidransky,et al.  Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. , 2002, Cancer research.

[5]  Diane D. Liu,et al.  Aberrant promoter methylation of multiple genes in bronchial brush samples from former cigarette smokers. , 2002, Cancer research.

[6]  M. Stroun,et al.  About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. , 2001, Clinica chimica acta; international journal of clinical chemistry.

[7]  L. Mariani,et al.  Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. , 2001, Cancer research.

[8]  J. Minna,et al.  5' CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. , 2001, Cancer research.

[9]  G. Pelosi,et al.  Immunoreactivity for Thyroid Transcription Factor-1 in Stage I Non–Small Cell Carcinomas of the Lung , 2001, The American journal of surgical pathology.

[10]  M. Muers,et al.  Genetic alterations in bronchial mucosa and plasma DNA from individuals at high risk of lung cancer , 2001, International journal of cancer.

[11]  C. Henschke.  Early lung cancer action project , 2000, Cancer.

[12]  J. Herman,et al.  Predicting lung cancer by detecting aberrant promoter methylation in sputum. , 2000, Cancer research.

[13]  A. Kraus,et al.  Differential frequencies of p16(INK4a) promoter hypermethylation, p53 mutation, and K-ras mutation in exfoliative material mark the development of lung cancer in symptomatic chronic smokers. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  P C Goodman,et al.  Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer. , 2000, Chest.

[15]  Y. Miller,et al.  Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[16]  S. Leung,et al.  Quantitative and temporal correlation between circulating cell-free Epstein-Barr virus DNA and tumor recurrence in nasopharyngeal carcinoma. , 1999, Cancer research.

[17]  U. Pastorino,et al.  Detection of microsatellite alterations in plasma DNA of non-small cell lung cancer patients: a prospect for early diagnosis. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  W. Prime,et al.  Genetic alterations in bronchial lavage as a potential marker for individuals with a high risk of developing lung cancer. , 1999, Cancer research.

[19]  J. Herman,et al.  Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. , 1999, Journal of the National Cancer Institute.

[20]  W. Travis,et al.  Histological Classification of Lung and Pleural Tumours , 1999 .

[21]  J. Herman,et al.  Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. , 1999, Cancer research.

[22]  T K Lau,et al.  Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. , 1998, American journal of human genetics.

[23]  J. Samet,et al.  Molecular damage in the bronchial epithelium of current and former smokers. , 1997, Journal of the National Cancer Institute.

[24]  M. Buyse,et al.  Immunocytochemical markers in stage I lung cancer: relevance to prognosis. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  J S Lee,et al.  Clonal genetic alterations in the lungs of current and former smokers. , 1997, Journal of the National Cancer Institute.

[26]  C. Mountain,et al.  Revisions in the International System for Staging Lung Cancer. , 1997, Chest.

[27]  K. Livak,et al.  Real time quantitative PCR. , 1996, Genome research.

[28]  A. Kurt,et al.  Microsatellite alterations in plasma DNA of small cell lung cancer patients , 1996, Nature Medicine.

[29]  C. Croce,et al.  The FHIT Gene at 3p14.2 Is Abnormal in Lung Cancer , 1996, Cell.

[30]  R Doll,et al.  Mortality from smoking worldwide. , 1996, British medical bulletin.

[31]  J. Herman,et al.  5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers , 1995, Nature Medicine.

[32]  Y S Erozan,et al.  Microsatellite alterations as clonal markers for the detection of human cancer. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Y. T. van der Schouw,et al.  ROC Curves and the Areas under Them for Dichotomized Tests , 1994, Medical decision making : an international journal of the Society for Medical Decision Making.

[34]  C. Harris,et al.  Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. , 1994, Cancer research.

[35]  R. Hruban,et al.  Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. , 1994, Cancer research.

[36]  U. Pastorino,et al.  Deletions of 17p and p53 mutations in preneoplastic lesions of the lung. , 1992, Cancer research.

[37]  P. Ganly,et al.  p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus. , 1992, Oncogene.

[38]  R. Ueda,et al.  Three distinct regions involved in 3p deletion in human lung cancer. , 1992, Oncogene.

[39]  R. Abramson,et al.  Detection of specific polymerase chain reaction product by utilizing the 5'----3' exonuclease activity of Thermus aquaticus DNA polymerase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[40]  B. Shapiro,et al.  Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease , 1983, Cancer.

[41]  B. Shapiro,et al.  Free DNA in the serum of cancer patients and the effect of therapy. , 1977, Cancer research.