Detection of chromosome 3p alterations in serum DNA of non-small-cell lung cancer patients

Sánchez-Céspedes, Montserrat; Monzó, Mariano; Rosell, Rafael; Pifarré, Alex; Calvo, Ran; López-Cabrerizo, M. Paz; Astudillo, I

doi:10.1023/a:1008230331221

Cited by 84 publications

(51 citation statements)

References 7 publications

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“…10,22,23 Genetic alteration rates of approximately 40% have been reported with this marker. 24,25 Combining the data from our 2 studies gives an overall genetic alteration rate of 33/108 (31%) for this marker in patients with lung cancer, which is consistent with the results of previous studies. High genetic alteration rates have also been reported at 3p21.3 and at the 8p chromosome.…”

Section: Discussionsupporting

confidence: 89%

Genetic abnormalities in plasma DNA of patients with lung cancer and other respiratory diseases

Khan¹,

Coulson²,

Woll³

2004

Intl Journal of Cancer

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The detection of tumour-associated genetic alterations in plasma DNA has been proposed as a simple method for the early diagnosis of lung cancer and for identifying individuals at high risk of lung cancer who might be included in screening or chemoprevention programmes. To evaluate the practicality of this approach, we screened a panel of 16 plasma DNA markers in a lung cancer population to identify those with the highest genetic alteration rate. These were then used to study plasma DNA in 206 hospital outpatients with lung cancer and other respiratory diseases. Plasma and lymphocyte DNA were isolated from blood samples collected from hospital outpatients. Polymerase chain reaction was carried out with 16 microsatellite markers covering chromosomal regions 3p, 8p, 9p, 13q and 17p, using DNA from 32 lung cancer patients. The 3 markers most commonly affected were selected for use in a larger study of 86 lung cancer patients and 120 patients with other respiratory diseases. In the pilot study, 3 primer pairs (D3S1300, D3S1560, D8S201) together detected genetic alterations in plasma DNA in 60% of lung cancer patients. In the larger study, significantly higher genetic alteration rates were observed in lung cancer patients than in patients with other respiratory diseases for the two markers D3S1560 and D8S201. The overall genetic alteration rate was 69% in the lung cancer patients and 42% in the patients with other respiratory diseases (p < 0.001). Analysis of plasma and lymphocyte DNA to detect genetic alterations typical of lung cancer is possible in large studies. The genetic alteration rate we found in lung cancer patients was comparable with other studies. Although the genetic alteration rate was significantly higher in the lung cancer than the respiratory disease patients, it did not have good positive predictive value in this population. Longitudinal studies are required to determine whether genetic changes in plasma DNA of non-cancer patients indicate a high risk of later lung cancer. © 2004 Wiley-Liss, Inc. Key words: biomarkers; diagnosis; screeningOne in five smokers dies prematurely from lung cancer. Groups at even higher risk can be identified, such as smokers from certain ethnic and occupational groups, carriers of polymorphisms in the cytochrome P450 1A1 gene and those already treated for primary lung cancer. Such groups have been targeted in trials of lung cancer screening, using chest X-rays, sputum cytology or spiral CT-scanning. 1,2 There is also increasing interest in primary and secondary chemoprevention programmes for high risk individuals using treatments such as ␤-carotene or metalloproteinase inhibitors, but none to date has been shown to be effective. 3,4 The possibility of developing a simple blood test to identify high risk individuals for lung cancer prevention and screening programmes is therefore attractive. 5 In lung cancer, as in most epithelial tumours, malignancy results from the accumulation of multiple genetic alterations, which can arise from deletions, mutations or changes in gen...

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Section: Discussionsupporting

confidence: 89%

Genetic abnormalities in plasma DNA of patients with lung cancer and other respiratory diseases

Khan¹,

Coulson²,

Woll³

2004

Intl Journal of Cancer

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“…The number of tumours checked and restriction enzymes used may influence this result. In studies reporting the same type of molecular changes in both tumour DNA and plasma DNA (Vasioukhin et al, 1994;Chen et al, 1996;Nawroz et al, 1996;Anker et al, 1997;Hibi et al, 1998;Sanchez-Cespedes et al, 1998), molecular markers have been selected that display a high rate of specific alterations. However, to our knowledge, exon 1 of p16 INK4a had not been utilized to date to check plasma DNA in breast cancer patients, and there are no available data concerning its informativeness.…”

Section: Discussionmentioning

confidence: 99%

“…More recent studies have involved the use of polymerase chain reaction (PCR) to amplify plasma DNA and identify genetic alterations in it that correspond to the same alterations found in tumour DNA. The sensitivity of PCR techniques in the detection of these alterations in plasma DNA may be as high as 86% (Anker et al, 1997); and the specificity shown in the studies in this field ranged from about 28% to 100% (Anker et al, 1997;Mulcahy et al, 1998;Sanchez-Cespedes et al, 1998). Among these alterations, K-ras, N-ras and p53 gene mutations have been reported in the plasma DNA of patients with pancreatic cancer, colorectal cancer and acute myelogenous leukaemia (Vasioukhin et al, 1994;Anker et al, 1997;Hibi et al, 1998).…”

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confidence: 99%

Aberrant DNA methylation of the p16INK4a gene in plasma DNA of breast cancer patients

et al. 1999

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Summary Hypermethylation of exon 1 of p16 INK4a was examined in tumour and plasma DNA of a series of breast cancer patients. De novo methylation was observed in the tumours of eight patients (23%), and in plasma DNA in five (14%) of these eight patients. Our data show that de novo methylation of exon 1 of p16 INK4a can be demonstrated in plasma DNA of breast cancer patients, a fact that provides additional evidence of the tumour-related origin of free plasma DNA in cancer patients.

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“…Some investigators have shown that testing for DNA alterations in peripheral blood has great potential, especially for early detection and diagnosis and for monitoring for a relapse during follow-up (Chen et al, 1996;Nawroz et al, 1996;Sozzi et al, 1999Sozzi et al, , 2001Cuda et al, 2000;Nunes et al, 2001). The same alterations which mean mutations, methylation, and loss of heterozygosity, in genomic DNA have been observed in DNA from both tumour cells in resected and biopsy specimens, and from serum samples in patients with various types of tumours, including NSCLC (Sanchez-Cespedes et al, 1998;Esteller et al, 1999). Some studies have even reported that genetic aberrations in serum DNA modulate survival in NSCLC patients treated with chemotherapy.…”

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confidence: 98%

Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA)

et al. 2007

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The aim of this study was to evaluate the usefulness of EGFR mutation status in serum DNA as a means of predicting a benefit from gefitinib (IRESSA) therapy in Japanese patients with non-small cell lung cancer (NSCLC). We obtained pairs of tumour and serum samples from 42 patients treated with gefitinib. EGFR mutation status was determined by a direct sequencing method and by Scorpion Amplification Refractory Mutation System (ARMS) technology. EGFR mutations were detected in the tumour samples of eight patients and in the serum samples of seven patients. EGFR mutation status in the tumours and serum samples was consistent in 39 (92.9%) of the 42 pairs. EGFR mutations were strong correlations between both EGFR mutation status in the tumour samples and serum samples and objective response to gefitinib (Po0.001). Median progression-free survival time was significantly longer in the patients with EGFR mutations than in the patients without EGFR mutations (194 vs 55 days, P ¼ 0.016, in tumour samples; 174 vs 58 days, P ¼ 0.044, in serum samples). The results suggest that it is feasible to use serum DNA to detect EGFR mutation, and that it's potential as a predictor of response to, and survival on gefitinib is worthy of further evaluation.

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Detection of chromosome 3p alterations in serum DNA of non-small-cell lung cancer patients

Cited by 84 publications

References 7 publications

Genetic abnormalities in plasma DNA of patients with lung cancer and other respiratory diseases

Genetic abnormalities in plasma DNA of patients with lung cancer and other respiratory diseases

Aberrant DNA methylation of the p16INK4a gene in plasma DNA of breast cancer patients

Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA)

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