Size distribution of circulating cell-free DNA in sera of breast cancer patients in the course of adjuvant chemotherapy

Deligezer, Ugur; Eralp, Yeşim; Akişık, Ebru E.; Akisik, Elif; Saip, Pınar; Topuz, Erkan; Dalay, Nejat

doi:10.1515/cclm.2008.080

Cited by 46 publications

(33 citation statements)

References 25 publications

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“…This could explain the contradictory results reported by the few previous studies on the clinical use of the integrity index to follow cancer progression that did not allow drawing general conclusions (i.e., estimation of ctDNA fragmentation was found lower [22], [23] equivalent [24], [25] or higher [13], [21], [26], [27] than in controls). As stated by Jung et al [28] those discrepancies might be related to pre-analytical and analytical factors as well as possible bias in the selection of the study groups.…”

Section: Discussionmentioning

confidence: 88%

High Fragmentation Characterizes Tumour-Derived Circulating DNA

et al. 2011

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BackgroundCirculating DNA (ctDNA) is acknowledged as a potential diagnostic tool for various cancers including colorectal cancer, especially when considering the detection of mutations. Certainly due to lack of normalization of the experimental conditions, previous reports present many discrepancies and contradictory data on the analysis of the concentration of total ctDNA and on the proportion of tumour-derived ctDNA fragments.MethodologyIn order to rigorously analyse ctDNA, we thoroughly investigated ctDNA size distribution. We used a highly specific Q-PCR assay and athymic nude mice xenografted with SW620 or HT29 human colon cancer cells, and we correlated our results by examining plasma from metastatic CRC patients.Conclusion/SignificanceFragmentation and concentration of tumour-derived ctDNA is positively correlated with tumour weight. CtDNA quantification by Q-PCR depends on the amplified target length and is optimal for 60–100 bp fragments. Q-PCR analysis of plasma samples from xenografted mice and cancer patients showed that tumour-derived ctDNA exhibits a specific amount profile based on ctDNA size and significant higher ctDNA fragmentation. Metastatic colorectal patients (n = 12) showed nearly 5-fold higher mean ctDNA fragmentation than healthy individuals (n = 16).

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Section: Discussionmentioning

confidence: 88%

High Fragmentation Characterizes Tumour-Derived Circulating DNA

et al. 2011

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“…The ccf tumor DNA detection seems to be more reliable for predicting relapse than the standard biomarker, carcinoembryonic antigen (CEA), used for the management of colorectal cancer [22]. It was also reported that the levels of ccf DNA could be changed after therapy in breast cancer [23,24]. The observations suggest that determination of ccf DNA in cancer may prove a useful tool in the management of the condition.…”

Section: Discussionmentioning

confidence: 99%

Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors

et al. 2009

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BackgroundWith the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA) seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been found in several cancer types and might have a diagnostic value.MethodsUsing multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic) curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters.ResultsWhile the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P < 0.001) and the healthy control group (P < 0.001), the level of ccf mtDNA was found to be significantly lower in the two tumor-groups (benign: P < 0.001; malignant: P = 0.022). The level of ccf nDNA was also associated with tumor-size (<2 cm vs. >2 cm<5 cm; 2250 vs. 6658; Mann-Whitney-U-Test: P = 0.034). Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P < 0.001) and between the tumor group and the healthy controls using ccf mtDNA as marker (cut-off: 463282 GE/ml; sensitivity: 53%; specificity: 87%; P < 0.001).ConclusionOur data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.

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“…The results of this first study were later confirmed in patients with lung cancer undergoing chemotherapy [55][56][57], in patients with rectal cancer receiving neoadjuvant radiochemotherapy [58], in patients with ovarian cancer treated by chemotherapy [59,60] and in patients with renal cancer treated by tyrosine kinase inhibitors [61]. However, it has to be mentioned that some minor studies with lower numbers of patients reported no association between cfDNA kinetics and tumor relapse or treatment response [37,62].…”

Section: Cfdnamentioning

confidence: 67%

CNAPS in Therapy Monitoring

Holdenrieder

2014

Advances in Predictive, Preventive and Personalised Medicine

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Monitoring of disease state and of therapy response is highly relevant for efficient patient management. Monitoring tools comprise observation of clinical signs and performing specific examinations such as imaging or blood analyses. This review focusses on the relevance of blood-based biomarker monitoring by circulating nucleic acids for diverse indications that is exemplified on patients who develop or suffer from cancer disease. These indications include (i) screening of patient groups who have a risk to develop a disease, (ii) monitoring response to local or systemic therapies in patients with a defined diagnosis and (iii) early detection of disease recurrence after the primary therapy has ended. Useful biomarkers have to fulfill the highest methodical, pre-analytical and clinical quality criteria and have to be implemented in standardized patient management procedures. The current situation of circulating nucleic acids is summarized on the levels of genetic, epigenetic, transcript, non-coding RNA and nucleosome markers and an outlook is presented as to how these markers can be integrated into a future strategy that enables a personalized management of the patients.

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Size distribution of circulating cell-free DNA in sera of breast cancer patients in the course of adjuvant chemotherapy

Abstract: Our findings suggest that non-apoptotic fragments contribute to a higher degree to the change of the DNA level during adjuvant chemotherapy.

Cited by 46 publications

References 25 publications

High Fragmentation Characterizes Tumour-Derived Circulating DNA

High Fragmentation Characterizes Tumour-Derived Circulating DNA

Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors

CNAPS in Therapy Monitoring

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