Gene Mutations in Circulating Tumour DNA as a Diagnostic and Prognostic Marker in Head and Neck Cancer—A Systematic Review

(1) Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies globally. An early diagnosis of this disease is crucial, and the detection of gene mutations in circulating tumour DNA (ctDNA) through a liquid biopsy is a promising non-invasive diagnostic method. This review aims to provide an overview of ctDNA mutations in HNSCC patients and discuss the potential use of this tool in diagnosis and prognosis. (2) Methods: A systematic search for articles published in the English language between January 2000 and April 2021 in the Medline and Scopus databases was conducted. (3) Results: A total of 10 studies published in nine publications were selected and analysed. Altogether, 390 samples were obtained from HNSCC patients, and 79 control samples were evaluated. The most often explored gene mutation in ctDNA was TP53. (4) Conclusions: The examination of a larger group of gene mutations and the use of a combination of multiple detection methods contribute to a higher detection rate of mutated ctDNA. More studies are necessary to verify these conclusions and to translate them into clinical practice.

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Investigation of urinary volatomic alterations in head and neck cancer: a non-invasive approach towards diagnosis and prognosis

Metabolomics ◽

10.1007/s11306-017-1251-6 ◽

2017 ◽

Vol 13 (10) ◽

Cited By ~ 13

Author(s):

Ravindra Taware ◽

Khushman Taunk ◽

Jorge A. M. Pereira ◽

Rahul Dhakne ◽

Narayanan Kannan ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Invasive Approach ◽

Non Invasive ◽

Diagnosis And Prognosis

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Role of Cardiac MRI in Detecting Familial Hypertrophic Cardiomyopathy: Review

Journal of Clinical and Health Sciences ◽

10.24191/jchs.v1i1.5846 ◽

2016 ◽

Vol 1 (1) ◽

pp. 4

Author(s):

Marymol Koshy ◽

Bushra Johari ◽

Mohd Farhan Hamdan ◽

Mohammad Hanafiah

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Magnetic Resonance ◽

Genetic Disorder ◽

Familial Hypertrophic Cardiomyopathy ◽

Non Invasive ◽

Wide Range ◽

Proper Diagnosis ◽

Magnetic Resonance Imaging Mri ◽

Potential Use

Hypertrophic cardiomyopathy (HCM) is a global disease affecting people of various ethnic origins and both genders. HCM is a genetic disorder with a wide range of symptoms, including the catastrophic presentation of sudden cardiac death. Proper diagnosis and treatment of this disorder can relieve symptoms and prolong life. Non-invasive imaging is essential in diagnosing HCM. We present a review to deliberate the potential use of cardiac magnetic resonance (CMR) imaging in HCM assessment and also identify the risk factors entailed with risk stratification of HCM based on Magnetic Resonance Imaging (MRI).

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Retinoblastoma genetics screening and clinical management

BMC Medical Genomics ◽

10.1186/s12920-021-01034-6 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Himika Gupta ◽

Sivasankar Malaichamy ◽

Ashwin Mallipatna ◽

Sakthivel Murugan ◽

Nallathambi Jeyabalan ◽

...

Keyword(s):

Clinical Management ◽

Detection Rate ◽

Mutation Detection ◽

Gene Mutations ◽

Disease Recurrence ◽

Germline Mutations ◽

Global Studies ◽

Mutation Detection Rate ◽

Gene Deletions

Abstract Background India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. Methods Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. Results Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. Conclusions We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

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Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽

10.3390/cancers13133373 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3373

Author(s):

Milena Matuszczak ◽

Jack A. Schalken ◽

Maciej Salagierski

Keyword(s):

Prostate Cancer ◽

Liquid Biopsy ◽

Current Knowledge ◽

Prostate Gland ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Digital Rectal Examination ◽

Cost Effective ◽

Non Invasive ◽

Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

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Effect of ATR Inhibition in RT Response of HPV-Negative and HPV-Positive Head and Neck Cancers

International Journal of Molecular Sciences ◽

10.3390/ijms22041504 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1504

Author(s):

Rüveyda Dok ◽

Mary Glorieux ◽

Marieke Bamps ◽

Sandra Nuyts

Keyword(s):

Head And Neck ◽

Ataxia Telangiectasia ◽

Cell Cycle Checkpoints ◽

Specific Cell ◽

Ataxia Telangiectasia Mutated ◽

Checkpoint Kinase 1 ◽

Hpv Status ◽

Damage Response ◽

Xenograft Models ◽

Potential Use

Radiotherapy (RT) has a central role in head and neck squamous cell carcinoma (HNSCC) treatment. Targeted therapies modulating DNA damage response (DDR) and more specific cell cycle checkpoints can improve the radiotherapeutic response. Here, we assessed the influence of ataxia-telangiectasia mutated and Rad3-related (ATR) inhibition with the ATR inhibitor AZD6738 on RT response in both human papillomavirus (HPV)-negative and HPV-positive HNSCC. We found that ATR inhibition enhanced RT response in HPV-negative and HPV-positive cell lines independent of HPV status. The radiosensitizing effect of AZD6738 was correlated with checkpoint kinase 1 (CHK1)-mediated abrogation of G2/M-arrest. This resulted in the inhibition of RT-induced DNA repair and in an increase in the percentage of micronucleated cells. We validated the enhanced RT response in HPV-negative and HPV-positive xenograft models. These data demonstrate the potential use of ATR inhibition in combination with RT as a treatment option for both HPV-negative and HPV-positive HNSCC patients.

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Analytical validation of an automated assay for the measurement of adenosine deaminase (ADA) and its isoenzymes in saliva and a pilot evaluation of their changes in patients with SARS-CoV-2 infection

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0324 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Lorena Franco-Martínez ◽

Fernando Tecles ◽

Alberto Torres-Cantero ◽

Enrique Bernal ◽

Indra San Lázaro ◽

...

Keyword(s):

Adenosine Deaminase ◽

Analytical Validation ◽

Mean Values ◽

Chemical Inactivation ◽

Non Invasive ◽

Automated Assay ◽

Coefficients Of Variation ◽

Recovery Percentage ◽

Triton X ◽

Potential Use

Abstract Objectives The aim of the present study was to validate a commercially available automated assay for the measurement of total adenosine deaminase (tADA) and its isoenzymes (ADA1 and ADA2) in saliva in a fast and accurate way, and evaluate the possible changes of these analytes in individuals with SARS-CoV-2 infection. Methods The validation, in addition to the evaluation of precision and accuracy, included the analysis of the effects of the main procedures that are currently being used for SARS-CoV-2 inactivation in saliva and a pilot study to evaluate the possible changes in salivary tADA and isoenzymes in individuals infected with SARS-CoV-2. Results The automated assay proved to be accurate and precise, with intra- and inter-assay coefficients of variation below 8.2%, linearity under dilution linear regression with R2 close to 1, and recovery percentage between 80 and 120% in all cases. This assay was affected when the sample is treated with heat or SDS for virus inactivation but tolerated Triton X-100 and NP-40. Individuals with SARS-CoV-2 infection (n=71) and who recovered from infection (n=11) had higher mean values of activity of tADA and its isoenzymes than healthy individuals (n=35). Conclusions tADA and its isoenzymes ADA1 and ADA2 can be measured accurately and precisely in saliva samples in a rapid, economical, and reproducible way and can be analyzed after chemical inactivation with Triton X-100 and NP-40. Besides, the changes observed in tADA and isoenzymes in individuals with COVID-19 open the possibility of their potential use as non-invasive biomarkers in this disease.

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A Modified Method to Isolate Circulating Tumor Cells and Identify by a Panel of Gene Mutations in Lung Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033821995275 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199527

Author(s):

Helin Wang ◽

Jieqing Wu ◽

Qi Zhang ◽

Jianqing Hao ◽

Ying Wang ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Detection Rate ◽

Target Genes ◽

White Blood Cells ◽

Gene Mutations ◽

Copy Number Variations ◽

Immunomagnetic Beads ◽

Membrane Rupture

The CellSearch system is the only FDA approved and successful used detection technology for circulating tumor cells(CTCs). However, the process for identification of CTCs by CellSearch appear to damage the cells, which may adversely affects subsequent molecular biology assays. We aimed to explore and establish a membrane-preserving method for immunofluorescence identification of CTCs that keeping the isolated cells intact. 98 patients with lung cancer were enrolled, and the efficacy of clinical detection of CTCs was examined. Based on the CellSearch principle, we optimized an anti-EpCAM antibody and improved cell membrane rupture. A 5 ml peripheral blood sample was used to enrich CTCs with EpCAM immunomagnetic beads. Fluorescence signals were amplified with secondary antibodies against anti-EpCAM antibody attached on immunomagnetic beads. After identifying CTCs, single CTCs were isolated by micromanipulation. To confirm CTCs, genomic DNA was extracted and amplified at the single cell level to sequence 72 target genes of lung cancer and analyze the mutation copy number variations (CNVs) and gene mutations. A goat anti-mouse polyclonal antibody conjugated with Dylight 488 was selected to stain tumor cells. We identified CTCs based on EpCAM+ and CD45+ cells to exclude white blood cells. In the 98 lung cancer patients, the detection rate of CTCs (≥1 CTC) per 5 ml blood was 87.76%, the number of detections was 1–36, and the median was 2. By sequencing 72 lung cancer-associated genes, we found a high level of CNVs and gene mutations characteristic of tumor cells. We established a new CTCs staining scheme that significantly improves the detection rate and allows further analysis of CTCs characteristics at the genetic level.

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