scholarly journals Liquid Biopsy as a Diagnostic and Prognostic Tool for Women and Female Dogs with Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5233
Author(s):  
Jucimara Colombo ◽  
Marina Gobbe Moschetta-Pinheiro ◽  
Adriana Alonso Novais ◽  
Bruna Ribeiro Stoppe ◽  
Enrico Dumbra Bonini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liquid Biopsy ◽  
Gene Mutations ◽  
Malignant Neoplasm ◽  
Genetic Variations ◽  
Highly Pathogenic ◽  
Genome Analysis Toolkit ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Introduction: Breast cancer (BC) is the malignant neoplasm with the highest mortality rate in women and female dogs are good models to study BC. Objective: We investigated the efficacy of liquid biopsy to detect gene mutations in the diagnosis and follow-up of women and female dogs with BC. Materials and Methods: In this study, 57 and 37 BC samples were collected from women and female dogs, respectively. After core biopsy and plasma samples were collected, the DNA and ctDNA of the tumor fragments and plasma were processed for next generation sequencing (NGS) assay. After preprocessing of the data, they were submitted to the Genome Analysis ToolKit (GATK). Results: In women, 1788 variants were identified in tumor fragments and 221 variants in plasma; 66 variants were simultaneously detected in tumors and plasma. Conversely, in female dogs, 1430 variants were found in plasma and 695 variants in tumor fragments; 59 variants were simultaneously identified in tumors and plasma. The most frequently mutated genes in the tumor fragments of women were USH2A, ATM, and IGF2R; in female dogs, they were USH2A, BRCA2, and RRM2. Plasma of women showed the most frequent genetic variations in the MAP3K1, BRCA1, and GRB7 genes, whereas plasma from female dogs had variations in the NF1, ERBB2, and KRT17 genes. Mutations in the AKT1, PIK3CA, and BRIP genes were associated with tumor recurrence, with a highly pathogenic variant in PIK3CA being particularly prominent. We also detected a gain-of-function mutation in the GRB7, MAP3K1, and MLH1 genes. Conclusion: Liquid biopsy is useful to identify specific genetic variations at the beginning of BC manifestation and may be accompanied over the entire follow-up period, thereby supporting the clinicians in refining interventions.

scholarly journals Methylmalonic Acidemia with Novel MUT Gene Mutations

2017 ◽  
Vol 2017 ◽  
pp. 1-2
Author(s):  
Inusha Panigrahi ◽  
Savita Bhunwal ◽  
Harish Varma ◽  
Simranjeet Singh
Keyword(s):  
Sanger Sequencing ◽  
Gene Mutations ◽  
Methylmalonic Acidemia ◽  
Feeding Problems ◽  
Novel Variants ◽  
Mut Gene ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Poor Weight Gain

A 5-year-old boy presented with recurrent episodes of fever, feeding problems, lethargy, from the age of 11 months, and poor weight gain. He was admitted and evaluated for metabolic causes and diagnosed as having methylmalonic acidemia (MMA). He was treated with vit B12 and carnitine supplements and has been on follow-up for the last 3 years. Mutation analysis by next generation sequencing (NGS), supplemented with Sanger sequencing, revealed two novel variants in the MUT gene responsible for MMA in exon 5 and exon 3, respectively. Recently he developed dystonic movements including orofacial dyskinesia. With advent of NGS, judicious use of NGS with Sanger sequencing can help identify causative possibly pathogenic mutations.

scholarly journals A DNA methylation-based liquid biopsy for triple-negative breast cancer

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Katrina Cristall ◽  
Francois-Clement Bidard ◽  
Jean-Yves Pierga ◽  
Michael J. Rauh ◽  
Tatiana Popova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Liquid Biopsy ◽  
Blood Test ◽  
Triple Negative ◽  
Superior Performance ◽  
Serum Samples ◽  
Clonal Hematopoiesis ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

AbstractHere, we present a next-generation sequencing (NGS) methylation-based blood test called methylation DETEction of Circulating Tumour DNA (mDETECT) designed for the optimal detection and monitoring of metastatic triple-negative breast cancer (TNBC). Based on a highly multiplexed targeted sequencing approach, this assay incorporates features that offer superior performance and included 53 amplicons from 47 regions. Analysis of a previously characterised cohort of women with metastatic TNBC with limited quantities of plasma (<2 ml) produced an AUC of 0.92 for detection of a tumour with a sensitivity of 76% for a specificity of 100%. mDETECTTNBC was quantitative and showed superior performance to an NGS TP53 mutation-based test carried out on the same patients and to the conventional CA15-3 biomarker. mDETECT also functioned well in serum samples from metastatic TNBC patients where it produced an AUC of 0.97 for detection of a tumour with a sensitivity of 93% for a specificity of 100%. An assay for BRCA1 promoter methylation was also incorporated into the mDETECT assay and functioned well but its clinical significance is currently unclear. Clonal Hematopoiesis of Indeterminate Potential was investigated as a source of background in control subjects but was not seen to be significant, though a link to adiposity may be relevant. The mDETECTTNBC assay is a liquid biopsy able to quantitatively detect all TNBC cancers and has the potential to improve the management of patients with this disease.

scholarly journals Jervell and Lange-Nielsen Syndrome due to a Novel Compound Heterozygous KCNQ1 Mutation in a Chinese Family

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yue Qiu ◽  
Sen Chen ◽  
Xia Wu ◽  
Wen-Juan Zhang ◽  
Wen Xie ◽  
...  
Keyword(s):  
Deaf Child ◽  
Gene Mutations ◽  
Deaf Children ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Qtc Interval ◽  
Cardiac Events ◽  
Life Threatening ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Jervell and Lange-Nielsen syndrome (JLNS) is a rare but severe autosomal recessive disease characterized by profound congenital deafness and a prolonged QTc interval (greater than 500 milliseconds) in the ECG waveforms. The prevalence of JLNS is about 1/1000000 to 1/200000 around the world. However, exceed 25% of JLNS patients suffered sudden cardiac death with kinds of triggers containing anesthesia. Approximately 90% of JLNS cases are caused by KCNQ1 gene mutations. Here, using next-generation sequencing (NGS), we identified a compound heterozygosity for two mutations c.1741A>T (novel) and c.477+5G>A (known) in KCNQ1 gene as the possible pathogenic cause of JLNS, which suggested a high risk of cardiac events in a deaf child. The hearing of this patient improved significantly with the help of cochlear implantation (CI). But life-threatening arrhythmias occurred with a trigger of anesthesia after the end of the CI surgery. Our findings extend the KCNQ1 gene mutation spectrum and contribute to the management of deaf children diagnosed with JLNS for otolaryngologists (especially cochlear implant teams).

scholarly journals Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1588 ◽  
Author(s):  
Sabrina Weber ◽  
Benjamin Spiegl ◽  
Samantha O. Perakis ◽  
Christine M. Ulz ◽  
Peter M. Abuja ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Reference Materials ◽  
Test Performance ◽  
Liquid Biopsy ◽  
Attractive Alternative ◽  
Routine Practice ◽  
Patients With Cancer ◽  
Technical Evaluation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Molecular profiling from liquid biopsy, in particular cell-free DNA (cfDNA), represents an attractive alternative to tissue biopsies for the detection of actionable targets and tumor monitoring. In addition to PCR-based assays, Next Generation Sequencing (NGS)-based cfDNA assays are now commercially available and are being increasingly adopted in clinical practice. However, the validity of these products as well as the clinical utility of cfDNA in the management of patients with cancer has yet to be proven. Within framework of the Innovative Medicines Initiative (IMI) program CANCER-ID we evaluated the use of commercially available reference materials designed for ctDNA testing and cfDNA derived from Diagnostic Leukaphereses (DLA) for inter- and intra-assay as well as intra- and inter-laboratory comparisons. In three experimental setups, a broad range of assays including ddPCR, MassARRAY and various NGS-based assays were tested. We demonstrate that both reference materials with predetermined VAFs and DLA samples are extremely useful for the performance assessment of mutation analysis platforms. Moreover, our data indicate a substantial variability of NGS assays with respect to sensitivity and specificity highlighting the importance of extensive validation of the test performance before offering these tests in clinical routine practice.

scholarly journals Molecular Profiling of Malignant Pleural Effusions with Next Generation Sequencing (NGS): Evidence that Supports Its Role in Cancer Management

2020 ◽  
Vol 10 (4) ◽  
pp. 206
Author(s):  
Georgia Ι. Grigoriadou ◽  
Stepan M. Esagian ◽  
Han Suk Ryu ◽  
Ilias P. Nikas
Keyword(s):  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Liquid Biopsy ◽  
Molecular Profiling ◽  
Pleural Effusions ◽  
Advanced Cancer Patients ◽  
Cancer Management ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Malignant pleural effusions (MPEs) often develop in advanced cancer patients and confer significant morbidity and mortality. In this review, we evaluated whether molecular profiling of MPEs with next generation sequencing (NGS) could have a role in cancer management, focusing on lung cancer. We reviewed and compared the diagnostic performance of pleural fluid liquid biopsy with other types of samples. When applied in MPEs, NGS may have comparable performance with corresponding tissue biopsies, yield higher DNA amount, and detect more genetic aberrations than blood-derived liquid biopsies. NGS in MPEs may also be preferable to plasma liquid biopsy in advanced cancer patients with a MPE and a paucicellular or difficult to obtain tissue/fine-needle aspiration biopsy. Of interest, post-centrifuge supernatant NGS may exhibit superior results compared to cell pellet, cell block or other materials. NGS in MPEs can also guide clinicians in tailoring established therapies and identifying therapy resistance. Evidence is still premature regarding the role of NGS in MPEs from patients with cancers other than lung. We concluded that MPE processing could provide useful prognostic and theranostic information, besides its diagnostic role.

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