Detection of genetic alterations in cfDNA as a possible strategy to monitor the neoplastic progression of Barrett's esophagus

Rumiato, Enrica; Boldrin, Elisa; Malacrida, Sandro; Realdon, Stefano; Fassan, Matteo; Morbin, T.; Battaglia, Giorgio; Amadori, Alberto; Saggioro, Daniela

doi:10.1016/j.trsl.2017.09.004

Cited by 18 publications

(19 citation statements)

References 31 publications

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“…Of note, an additional two patients displayed deletions, although they only had Barrett's metaplasia, but had instead developed other neoplasia: one primary bladder cancer in a polyp and one dysplastic duodenal polyp. Thus, the deletion analysis of ctDNA was not specific for GEAC .…”

Section: Can Ctdna Be Used To Distinguish Benign From Malignant Lesions?mentioning

confidence: 99%

“…Therefore, we recommend that all findings in plasma DNA are also tested in leucocyte DNA from the same patient in order to exclude CH. Furthermore, since some genetic aberrations are common to many cancer types, a detected aberration may not necessarily derive from the cancer type screened for in the study [69,78]. Thus, further technical developments together with improved knowledge of tumour biology are required in order to design assays based on ctDNA and correctly interpret findings.…”

Section: Difficulties and Limitations Of Ctdna Analysismentioning

confidence: 99%

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Cell‐free tumour DNA testing for early detection of cancer – a potential future tool

et al. 2019

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In recent years, detection of cell‐free tumour DNA (ctDNA) or liquid biopsy has emerged as an attractive noninvasive methodology to detect cancer‐specific genetic aberrations in plasma, and numerous studies have reported on the feasibility of ctDNA in advanced cancer. In particular, ctDNA assays can capture a more ‘global’ portrait of tumour heterogeneity, monitor therapy response, and lead to early detection of resistance mutations. More recently, ctDNA analysis has also been proposed as a promising future tool for detection of early cancer and/or cancer screening. As the average proportion of mutated DNA in plasma is very low (0.4% even in advanced cancer), exceedingly sensitive techniques need to be developed. In addition, as tumours are genetically heterogeneous, any screening test needs to assay multiple genetic targets in order to increase the chances of detection. Further research on the genetic progression from normal to cancer cells and their release of ctDNA is imperative in order to avoid overtreating benign/indolent lesions, causing more harm than good by early diagnosis. More knowledge on the sources and elimination of cell‐free DNA will enable better interpretation in older individuals and those with comorbidities. In addition, as white blood cells are the major source of cell‐free DNA in plasma, it is important to distinguish acquired mutations in leukocytes (benign clonal haematopoiesis) from an upcoming haematological malignancy or other cancer. In conclusion, although many studies report encouraging results, further technical development and larger studies are warranted before applying ctDNA analysis for early cancer detection in the clinic.

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Section: Can Ctdna Be Used To Distinguish Benign From Malignant Lesions?mentioning

confidence: 99%

Section: Difficulties and Limitations Of Ctdna Analysismentioning

confidence: 99%

Cell‐free tumour DNA testing for early detection of cancer – a potential future tool

et al. 2019

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“…Circulating tumor DNA was used for monitoring therapeutic effect and prognostic prediction in treatment of malignancy because of ctDNA level in advanced stage tumor [36] .The levels of detected ctDNA increase correlate with the malignant progression [37,13] . Low level of ctDNA in early stage tumor makes the detection difficult.…”

Section: Discussionmentioning

confidence: 99%

RNF213 gene mutation of circulating tumor DNA in early diagnosis of NSCLC using targeted next-generation sequencing

Jiang¹,

Zhao²,

P³

et al. 2019

Preprint

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Introduction To distinguish early stage lung cancer from benign disease of the lung nodules, especially the lesions with ground-glass opacity (GGO) or ground-glass nodule (GGN), we assessed gene mutations of the ctDNA in peripheral blood by using targeted next-generation sequencing (NGS). Methods Single lung nodule patients without mediastinal lymph nodes or symptoms hardly diagnosed by chest CT and biomarker of lung cancer were enrolled. All patients received minimally invasive surgery but refused preoperative biopsy. Gene mutations of pre-operative blood samples were detected by targeted NGS. Mutations with statistical differences were screened in lung cancer and benign disease grouped by postoperative pathology. Gene expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood. Results In training set, RNF213, KMT2D, CSMD3 and LRP1B genes mutated more frequently in early stage lung cancer (25cases) than benign nodules (18cases) (P<0.05). High expressions of RNF213 gene in lung cancers and low expressions in benign diseases were evaluated by immunohistochemistry. RNF213 gene mutated in 25% lung cancer samples in the validation set of 28 samples and showed high specificity (100%) and low sensibility (25.9%). In GGO and GGN patients, RNF213 mutated more frequently in early stage lung cancer compared to benign diseases (P<0.05). Conclusions RNF213 gene mutation was observed more frequently in early stage lung cancer, but rather than benign nodules. Mutation of RNF213 gene in peripheral blood may be a high specificity biomarker and valuable for early diagnosis of lung cancer.

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“…Locations of MSs and primer sequences were obtained from the UCSC Genome Browser (Human December 2013 GRCh38/hg38 Assembly). PCR primers and conditions have been previously described [22]. Forward primers were 5 -end labeled with FAM or HEX fluorescent dies (Sigma-Aldrich, Milan, Italy) and PCR products were analyzed using the 3730xl DNA analyzer (Life Technologies, Monza, Italy).…”

Section: Loh and Msi Analysismentioning

confidence: 99%

Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients

Boldrin

Nardo

Zulato

et al. 2019

IJMS

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Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays.

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Detection of genetic alterations in cfDNA as a possible strategy to monitor the neoplastic progression of Barrett's esophagus

Cited by 18 publications

References 31 publications

Cell‐free tumour DNA testing for early detection of cancer – a potential future tool

Cell‐free tumour DNA testing for early detection of cancer – a potential future tool

RNF213 gene mutation of circulating tumor DNA in early diagnosis of NSCLC using targeted next-generation sequencing

Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients

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