Methylation patterns and K-ras mutations in tumor and paired serum of resected non-small-cell lung cancer patients

Ramirez, José Luis; Sarries, Carme; Castro, Pedro López de; Roig, Bárbara; Queralt, Cristina; Escuín, Daniel; Aguirre, Itziar de; Sánchez, José Miguel; Manzano, José Luís; Margelı́, Mireia; Sánchez, José Javier; Astudillo, J.; Tarón, Miquel; Rosell, Rafael

doi:10.1016/s0304-3835(02)00740-1

Cited by 109 publications

(82 citation statements)

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“…Moreover, circulating DNA found in serum harbors the same genetic characteristics that are observed in paired tumor DNA, as reported by several authors. 17,18,28 We detected aberrant methylation of some of the 4 genes studied in patients with malignant tumors but detected 0% frequency in both fluids tested in the control group. These findings are along the same lines as the findings reported by other authors.…”

Section: Discussionmentioning

confidence: 83%

“…27 In the current study, tumor tissue was not available for every patient. However, it has been demonstrated that the presence of promoter methylation of various genes in bronchoalveolar lavage 19,24 and serum 17,18 is a surrogate for methylation of the same genes in tumor tissue. Moreover, circulating DNA found in serum harbors the same genetic characteristics that are observed in paired tumor DNA, as reported by several authors.…”

Section: Discussionmentioning

confidence: 99%

“…10 It has been observed that RARb, 11 RASSF1A, 12 p16/INK4a, 13 and DAPK 14 harbor hypermethylated promoters in 15% to 45% of solid tumors, 15 and hypermethylation changes may be excellent tumor markers. 16 Recent publications also have demonstrated the presence of promoter hypermethylation of various genes in bodily fluids, including serum, 17,18 bronchoalveolar lavage from patients with lung cancer, 19 sputum, 20 and pleural fluid. 21 The methylation-specific polymerase chain reaction (PCR) technique (MSP) is highly sensitive and can detect 0.1% tumor DNA from a heterogeneous cell population.…”

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confidence: 99%

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Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion

Benlloch

Galbis-Caravajal

Martín

et al. 2006

Cancer

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BACKGROUND.The objective of this study was to investigate the diagnostic value of methylation profiles for discrimination between malignant and benign pleural effusions. A secondary objective was to examine the concordance of methylation in samples of serum and pleural fluid.METHODS.The authors used methylation‐specific polymerase chain reaction (MSP) analysis to examine the promoter methylation status of 4 genes in patients with pleural effusion: death‐associated protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid receptor β (RARβ), and p16/INK4a. Pleural effusions were collected from 87 patients who had their diagnoses confirmed on cytologic and/or histologic examinations and clinical evolution. Pleural effusions were classified as malignant (n = 53 patients) or benign (n = 34 patients).RESULTS.Methylation was detected in serum from 45.3% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions, and it was detected in pleural fluid samples from 58.5% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions (P = .001). The sensitivity of MSP was greater than that of cytologic examination alone (39.1%; P = .001). When MSP was used together with cytologic examination, sensitivity increased to 69.8% (P = .001).CONCLUSIONS.Cell‐free methylated DNA in pleural fluid can be detected in patients with neoplastic malignancy in a single extraction by thoracocentesis. Adequate management of the extracted pleural fluid can provide a rapid and reliable diagnosis in patients with pleural effusions who have suspected malignancy. MSP, used together with cytologic examination, may obviate the need for other invasive diagnostic tests. Cancer 2006. © 2006 American Cancer Society.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion

Benlloch

Galbis-Caravajal

Martín

et al. 2006

Cancer

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“…Total number of patients: 989. Cho,1997Graziano,1999Grossi, 2003Huang,1998Keohavong,1996Kern,1994Kwiatkowski,1998Mitsdudomi,1991Nelson,1999Nemunaitis,1998Ramirez, 2003Rodenhuis,1997Rosell,1993Rosell,1997Schiller, 2001Siegfried,1997Silini,1994Slebos,1990Sugio,1992Tomizawa,2002Wang,1998 0.0 2.5 5.0 7.5 10.0…”

Section: Discussionmentioning

confidence: 99%

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

et al. 2004

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The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with metaanalysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using metaanalytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16 -1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26 -2.02) and in studies using PCR (HR 1.40; 95% CI 1.18 -1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86 -1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR.

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“…It was reported that genetic and epigenetic alterations in serum DNA (such as point mutation, gene amplification, loss of heterozygosity, microsatellite instability, and aberrant methylation) are identical to those found in primary human cancers [20][21][22][23][24] . Because the promoter methylation status of TSGs in primary tumors and matched serum samples was consistent with each other [4,25,26] , promoter hypermethylation of TSGs in serum DNA may become a promising biomarker for gastric and colorectal cancers.…”

Section: Introductionmentioning

confidence: 99%

Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients

Wang¹,

Yu²,

Liu³

et al. 2008

WJG

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AIM:To evaluate the diagnostic role of serum RASSF1Apromoter hypermethylation in gastric and colorectal adenocarcinoma. METHODS:Methylation-specific polymerase chain reaction (MSPCR) was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease (30 with benign gastric disease and 30 with benign colorectal disease), and 30 healthy donor controls. A paired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postoperative serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy. RESULTS:The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric (34.0%) and colorectal (28.9%) adenocarcinoma patients were significantly higher than those in patients with benign gastric (3.3%) or colorectal (6.7%) disease or in healthy donors (0%) (P < 0.01). The methylation status of Wang YC, Yu ZH, Liu C, Xu LZ, Yu W, Lu J, Zhu RM, Li GL, Xia XY, Wei XW, Ji HZ, Lu H, Gao Y, Gao WM, Chen LB. Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients.

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Methylation patterns and K-ras mutations in tumor and paired serum of resected non-small-cell lung cancer patients

Cited by 109 publications

References 17 publications

Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion

Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients

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