Increased integrity of circulating cell-free DNA in plasma of patients with acute leukemia

Gao, Yujie; He, Yujuan; Yang, Zailin; Shao, Hui-Yuan; Zuo, Yan; Bai, Yilong; Chen, Hui; Chen, Xianchun; Qin, Fengxian; Tan, Shi; Wang, Jian; Wang, Li; Zhang, Ling

doi:10.1515/cclm.2010.311

Cited by 62 publications

(47 citation statements)

References 25 publications

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“…Nonetheless, there are a number of inconsistencies in the literature in this area. Studies have reported the presence of longer DNA in the plasma of cancer patients (22)(23)(24)(25), whereas others reported higher prevalence of cancer-associated DNA mutations among the shorter plasma DNA molecules (14,27,40). This study was hence designed with an intent to explore the plasma DNA size profile of HCC patients in a high-resolution and comprehensive manner, which may shed light on the mechanisms related to the generation or release of plasma DNA by tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, previous studies on the size of circulating DNA in cancer patients gave inconsistent results. Studies have demonstrated that the overall integrity of circulating DNA would increase in cancer patients compared with subjects without a malignant condition (22)(23)(24)(25). Using PCR with different amplicon sizes, it was shown that the proportion of longer DNA would be higher in cancer patients.…”

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confidence: 99%

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Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

Jiang

Chan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

571

522

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The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z-score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.tumor markers | circulating tumor DNA | liquid biopsy | massively parallel sequencing | mitochondrial DNA A nalysis of circulating cell-free DNA has been increasingly used for the detection and monitoring of cancers (1-5). Different cancer-associated molecular characteristics, including copy number aberrations (6-9), methylation changes (10-13), single-nucleotide mutations (6, 14-17), cancer-derived viral sequences (18,19), and chromosomal rearrangements (20, 21), can be detected in the plasma of patients with various types of cancers. Despite the rapid expansion of clinical applications, many fundamental molecular characteristics of circulating DNA in cancer patients remain unclear. In particular, previous studies on the size of circulating DNA in cancer patients gave inconsistent results. Studies have demonstrated that the overall integrity of circulating DNA would increase in cancer patients compared with subjects without a malignant condition (22-25). Using PCR with different amplicon sizes, it was shown that the proportion of longer DNA would be higher in cancer patients. This aberration in DNA integrity was shown to be reversible after treatment, and the persistence of such changes was associated with poor prognosis (22, 26). On the other hand, there is also seemingly contradictory evidence that circulating DNA derived from t...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

Jiang

Chan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

571

522

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“…In contrast, cell-free DNA released from tumor cells varies in size due to necrosis, apoptosis, autophagy, or mitotic catastrophe (Jin and El-Deiry 2005;Jahr et al 2001), which generates a spectrum of DNA fragments with different strand lengths longer than 200 bp (Jahr et al 2001). Recently, it was shown that integrity of circulating DNA, measured as the ratio of longer to shorter DNA fragments, is higher in cancer patients than in normal individuals (Gao et al 2010;Wang et al 2003;Naoyuki et al 2006;Umetani et al 2006). However, the change in the physical properties of circulating cell-free DNA in glioma patients has not been completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Free DNA Quantification in Serum and Cerebrospinal Fluid in Glioma Patients

Shi

et al. 2011

J Mol Neurosci

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Unlike uniformly truncated DNA released from apoptotic nondiseased cells, free DNA released from dead tumor cells varies in size. Free DNA has been considered as a candidate biomarker for malignant tumors. We obtained serum samples from 70 patients with glioma and 22 healthy volunteers as control and cerebrospinal fluid (CSF) samples from 20 patients with glioma and eight nonneoplastic controls with hydrocephalus or arachnoid cyst and performed preoperative analysis of free DNA concentration and integrity by a quantitative polymerase chain reaction. With two primers sets amplifying short and long free DNA fragments (ALU115 and ALU247), free DNA integrity was determined by ratio of the concentration of ALU247 over ALU115 (ALU247/115). Our results indicate that free DNA integrity and the ratio of long fragments to short fragments may be a useful diagnostic assay for glioma. In summary, the CSF-free DNA concentration and integrity may serve as a new marker for the diagnosis of glioma.

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“…Indeed, Wang et al [85] reported a higher cfDNA integrity in cancer patients using 400 bp and 100 bp DNA amplicons. These results were confirmed with different amplicon sizes in breast [86], colorectal [87,88], esophageal [89], prostate [90], head and neck [91], nasopharyngeal cancer [92], melanoma [93] and acute leukemias [94] while cfDNA integrity was not elevated in other studies on prostate [95], lung [96,97] and breast cancer [98]. In addition, a few studies also found some prognostic relevance of cfDNA integrity for bladder [99], prostate [100], breast [86] and nasopharyngeal cancer [92].…”

Section: Cfdna Integritymentioning

confidence: 61%

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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Increased integrity of circulating cell-free DNA in plasma of patients with acute leukemia

Abstract: Our preliminary data suggest that plasma DNA integrity is increased in acute leukemia and may be a potential biomarker for monitoring MRD. However, more work is needed.

Cited by 62 publications

References 25 publications

Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

Prognostic Value of Free DNA Quantification in Serum and Cerebrospinal Fluid in Glioma Patients

CNAPS in Therapy Monitoring

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