Predictive Utility of Circulating Methylated DNA in Serum of Melanoma Patients Receiving Biochemotherapy

Mori, Takuji; O’Day, Steven; Umetani, Naoyuki; Martinez, Steve R.; Kitago, Minoru; Koyanagi, Kazuo; Kuo, Calvin; Takeshima, Teh Ling; Milford, Robert; Wang, He Jing; Vu, Vu D.; Nguyen, Sandy L.; Hoon, Dave S.B.

doi:10.1200/jco.2005.02.9876

Cited by 156 publications

(146 citation statements)

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“…In patients with malignancies, aberrant methylation of serum DNA has been reported (Müller et al, 2003;Ibanez de Caceres et al, 2004;Fiegl et al, 2005;Mori et al, 2005;Koyanagi et al, 2006). We have detected cell-free tumour DNA in serum of neuroblastoma patients (Gotoh et al, 2005).…”

Section: Discussionmentioning

confidence: 51%

“…The presence of tumour-derived DNA within the blood stream has been identified earlier (Müller et al, 2003;Fiegl et al, 2005;Mori et al, 2005). Recently, one study showed that the detection of circulating tumour cells was correlated with tumour-related methylated DNA in patients with melanoma (Koyanagi et al, 2006), suggesting that circulating tumour cells are a potential source of circulating methylated DNA.…”

Section: Discussionmentioning

confidence: 90%

“…A number of studies have evaluated the potential of circulating tumour-related methylated DNA in serum for the molecular diagnosis and prognosis of various types of cancer (Müller et al, 2003;Ibanez de Caceres et al, 2004;Mori et al, 2005). Methylation-specific PCR assay is a sensitive and specific assay for tumour-related DNA methylation in serum.…”

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confidence: 99%

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RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a prognostic marker

et al. 2009

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The tumour suppressor gene RASSF1A is known to be frequently silenced by promoter hypermethylation in neuroblastoma tumours. Here we explored the possible prognostic significance of aberrant promoter hypermethylation of RASSF1A in serum DNA samples of patients with neuroblastoma as a surrogate marker for circulating tumour cells. We analysed the methylation status of the RASSF1A gene in matched tumour and pretreatment serum DNA obtained from 68 neuroblastoma patients. Hypermethylation of RASSF1A in tumour samples was found in 64 patients (94%). In contrast, serum methylation of RASSF1A was observed in 17 patients (25%). Serum methylation of RASSF1A was found to be statistically associated with age X12 months at diagnosis (P ¼ 0.002), stage 4 (Po0.001) and MYCN amplification (Po0.001). The influence of serum RASSF1A methylation on prognosis was found to be comparable with that of the currently most reliable marker, MYCN amplification on univariate analysis (hazard ratio, 9.2; 95% confidence interval (CI), 2.8 -30.1; Po0.001). In multivariate analysis of survival, methylation of RASSF1A in serum had a hazard ratio of 2.4 (95% CI, 0.6 -9.2), although this association did not reach statistical significance (P ¼ 0.194). These findings show that the methylation status of RASSF1A in the serum of patients with neuroblastoma has the potential to become a prognostic predictor of outcome.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 90%

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RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a prognostic marker

et al. 2009

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“…16 Circulating cell free tumor DNA has been detected in plasma and serum by assessing allelic imbalance at microsatellite markers [17][18][19] and tumor-related gene methylation. [20][21][22] Recent studies indicate that these markers may show a predictive value of the response to biochemotherapy in stage IV patients. 23,24 Here, we report the results of a pilot study aimed at evaluating the BRAFV600E mutation as a molecular marker in circulating DNA from cutaneous melanoma patients.…”

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confidence: 99%

Detection of mutated BRAFV600E variant in circulating DNA of stage III–IV melanoma patients

Daniotti

Vallacchi

Rivoltini

et al. 2007

Intl Journal of Cancer

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BRAFV600E is the most represented somatic point mutation in cutaneous melanoma, thus providing a unique molecular marker for this disease. The development of efficient methods for its detection in free circulating DNA of patients may lead to the improvement of diagnostic and prognostic tools. With this aim, we evaluated whether BRAFV600E represents a detectable marker in the plasma/serum from melanoma patients in a pilot study. Circulating cell‐free DNA was extracted from the serum or plasma of 15 healthy donors and 41 melanoma patients at different clinical stages and obtained either presurgery or after surgery during follow‐up. Quantitative analysis showed higher levels of circulating free DNA in patients compared to controls, with the highest levels detected in samples obtained presurgery and at stage IV. Four different PCR methods were compared for their capacity to amplify a few copies of BRAFV600E in wild‐type DNA. BRAFV600E was detectable in circulating DNA of 12 patients and in none of the controls; only 1 PCR method reproducibly amplified BRAFV600E. Positive samples were obtained from 8/13 patients at stage IV and from 4/24 patients at stage III, but not in 4 patients at stage I–II; half of the positives were obtained presurgery and half at follow‐up. Correspondence between circulating DNA and related tumors were examined for 20 patients, and a correlation was found for stage IV patients. In conclusion, this method can be utilized for monitoring the disease in stage IV melanoma patients but it appears unsatisfactory for the early detection of melanoma. © 2007 Wiley‐Liss, Inc.

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“…For example, detection of methylated DNA from the MYOD1 CpG island is associated with reduced disease-free and overall survival in cervical cancer . Similarly, detection of circulating methylated DNA in the serum of patients with melanoma has prognostic value (Mori et al, 2005). The other area in which epigenetics has great clinical potential is in the early detection of cancer relapse in routine patient followup.…”

Section: Epigenomic Profiles As Markers Of Tumour Prognosismentioning

confidence: 99%

The context and potential of epigenetics in oncology

et al. 2009

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Cancer has long been known to be a disease caused by alterations in the genetic blueprint of cells. In the past decade it has become evident that epigenetic processes have a function, at least equally important, in neoplasia. Epigenetics describes the mechanisms that result in heritable alterations in gene expression profiles without an accompanying change in DNA sequence. Genetics and epigenetics intricately interact in the pathogenesis of cancer ( Esteller, 2007 ). In this review, we paint a broad picture of current understanding of epigenetic changes in cancer cells and reflect on the immense clinical potential of emerging knowledge of epigenetics in the diagnosis, prognostic assessment, treatment, and screening of cancer.

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Predictive Utility of Circulating Methylated DNA in Serum of Melanoma Patients Receiving Biochemotherapy

Abstract: Detection of circulating methylated DNA in serum can predict response to BC and disease outcome.

Cited by 156 publications

References 42 publications

RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a prognostic marker

RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a prognostic marker

Detection of mutated BRAFV600E variant in circulating DNA of stage III–IV melanoma patients

The context and potential of epigenetics in oncology

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