Concordance analysis between liquid biopsy (ctDNA) and tumor DNA molecular profiles from panel-based next-generation sequencing

Font, Natalia Rodon; Garbarino, Yessica No; Castello, Olga Díaz; Amoros, Juan Moya; Sánchez, Pedro Barrios; Lletget, David Coroleu; Cabello, Ma Antonia Lequerica; Marcet, Joan Borras; Meca, Sandra Mecho; Escape, Isabel; Martinez-Agea, Javier; García, Estefanía; Ferrer, Marta; Torrus, Xavier Puig

doi:10.1016/j.patol.2022.01.001

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…The concordance between tissue and plasma was approximately 75% when the KRAS gene was analyzed, as previously observed. In an earlier study, Rodon et al [12] found a 76.5% concordance of genotyping results using NGS in 18 tissue and blood samples of patients with locally advanced CRC or mCRC. Similarly, Erve et al [14] observed a 93% concordance between tumoral tissue DNA (ttDNA) and liquid biopsy RAS/BRAF ctDNA in their analysis of 100 sCRC patients with liver metastases.…”

Section: Discussionmentioning

confidence: 93%

“…However, the series of patients studied was not homogeneous since it included patients with synchronous and metachronous metastases. In addition, they did not determine the mutational status of the genes using liquid biopsy techniques, which could resolve the possible genetic heterogeneity present in this type of tumor and find other genetic lesions present in the metastatic samples [12]. In this regard, several studies that have explored ctDNA levels in mCRC have indicated that elevated ctDNA levels are correlated with poorer survival.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival

Sayagués,

Montero,

Jiménez-Pérez

et al. 2023

IJMS

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Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25–30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed the mutations of RAS, PIK3CA and BRAF genes in circulating tumor DNA (ctDNA) and tumoral tissue DNA (ttDNA) from 51 synchronous metastatic colorectal carcinoma (SMCC) patients by real-time PCR, and their relationship with the clinical, biological and histological features of disease at diagnosis. The highest frequency of mutations detected was in the KRAS gene, in tumor biopsies and plasma samples, followed by mutations of the PIK3CA, NRAS and BRAF genes. Overall, plasma systematically contained those genetic abnormalities observed in the tumor biopsy sample from the same subject, the largest discrepancies detected between the tumor biopsy and plasma from the same patient being for mutations in the KRAS and PIK3CA genes, with concordances of genotyping results between ttDNA and ctDNA at diagnosis of 75% and 84%, respectively. Of the 51 SMCC patients in the study, 25 (49%) showed mutations in at least 1 of the 4 genes analyzed in patient plasma. From the prognostic point of view, the presence and number of the most common mutations in the RAS, PIK3CA and BRAF genes in plasma from SMCC patients are independent prognostic factors for OS. Determination of the mutational status of ctDNA in SMCC could be a key tool for the clinical management of patients.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival

Sayagués,

Montero,

Jiménez-Pérez

et al. 2023

IJMS

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“…To date, this is the first study to our knowledge to compare ctDNA alterations with both matched primary and metastatic ESCC tumors; we now demonstrate that ctDNA captures both interheterogeneity and intraheterogeneity. Concordance of alterations between ctDNA and tissue in our cohort is comparable to previous cancer studies . Any discordance may be attributed to FFPE quality, spatial and temporary tumor heterogeneity, different sequencing depth, and low levels of ctDNA in early-stage disease .…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

Ng,

Ko,

Lam

et al. 2023

JAMA Surg

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ImportanceEsophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease.ObjectiveTo examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival.Design, Setting, and ParticipantsThis single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes.InterventionPatients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT).Main Outcomes and MeasuresDetection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS).ResultsA total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 10−6), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre–cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 10−4).Conclusions and RelevanceThe findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.

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Clinical Utility of Circulating Tumor DNA for Detecting Lung Cancer Mutations by Targeted Next‐Generation Sequencing With Insufficient Tumor Samples

Sun,

Zhang,

Yang

et al. 2024

Clinical Laboratory Analysis

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BackgroundCirculating tumor deoxyribonucleic acid (ctDNA) is increasingly applied in clinical practice. This study aimed to explore clinical utility of a minimal invasive and sensitive way of ctDNA for next‐generation sequencing in non–small cell lung cancer (NSCLC) with inadequate tumor samples.MethodsTargeted DNA sequencing was performed on tissue biopsies and matched plasma samples from 60 patients with NSCLC.ResultsA total of 13 driving genes were detected in 60 matched tissue DNA (tDNA) and ctDNA samples. Overall concordance rate was 75.47%, with 77.55% sensitivity and 50% specificity. Epidermal growth factor receptor (EGFR) mutations were the most common in both tDNA and ctDNA samples. Among other mutated genes were tumor protein p53 (TP53), erb‐b2 receptor tyrosine kinase 2 (ERBB2), anaplastic lymphoma kinase (ALK), cyclin‐dependent kinase inhibitor 2A (CDKN2A), ros proto‐oncogene 1, and receptor tyrosine kinase (ROS1). Mutations in b‐raf proto‐oncogene, serine/threonine kinase (BRAF), cluster of differentiation 274 (CD274), neurotrophin receptor tyrosine kinase 1 (NTRK1), and rearranged during transfection (RET) occurred only in plasma. The majority of mutations in both samples were single‐nucleotide variants. Deletions were found in EGFR, BRAF, and TP53 in ctDNA, whereas in tDNA, deletions were only found in EGFR. In ALK, single nucleic acid‐site amplification occurred simultaneously in tissue and plasma, but insertions and copy number variations were detected only in plasma.ConclusionsIdentifying ctDNA mutations by targeted sequencing in plasma is feasible, showing the clinical value of ctDNA‐targeted sequencing in NSCLC patients when tumor tissue sampling is insufficient or even impossible.

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Concordance analysis between liquid biopsy (ctDNA) and tumor DNA molecular profiles from panel-based next-generation sequencing

Cited by 4 publications

References 18 publications

Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival

Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

Clinical Utility of Circulating Tumor DNA for Detecting Lung Cancer Mutations by Targeted Next‐Generation Sequencing With Insufficient Tumor Samples

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