Next generation sequencing and rare genetic variants: From human population studies to medical genetics

2013 ◽  
Vol 54 (7) ◽  
pp. 518-532 ◽  
Author(s):  
Giuseppe Matullo ◽  
Cornelia Di Gaetano ◽  
Simonetta Guarrera
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Human Population ◽  
Population Studies ◽  
Medical Genetics ◽  
Next Generation ◽  
Rare Genetic Variants ◽  
Generation Sequencing

scholarly journals Assay of frequency and spectrum of genetic variants in TTN in healthy russian population

2021 ◽  
Vol 8 (5) ◽  
pp. 29-37
Author(s):  
Yu. A. Vakhrushev ◽  
A. A. Kozyreva ◽  
S. V. Zhuk ◽  
O. P. Rotar ◽  
A. A. Kostareva
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Sanger Sequencing ◽  
Heart Diseases ◽  
Genetic Research ◽  
Russian Population ◽  
Next Generation ◽  
Data Bases ◽  
International Data ◽  
Generation Sequencing

Background. Gene TTN associated with all types of cardiomyopathy, however its large size (294 b.p.) warrants a lot of individual unique genetic variants or variants with low frequency, that aggravates their interpretation. Besides that nowadays there is no data about spectrum of variants in this gene in healthy Russian population. Recognition frequency and spectrum of variants in gene TTN in healthy Russian population will allow us to use it for interpretation results of molecular genetic research for patients with different heart pathology, and define prognosis for different heart diseases.Objective. Recognize frequency and spectrum of single nucleotide and truncating variants in gene TTN in healthy Russian population and compare it with international data bases, and evaluate level of pathogenicity these variants and their distributing across titin structure.Design and methods. 192 men in age 55,8±6,6 years were tested with next-generation sequencing. Identified genetic variants were confirmed by Sanger sequencing. Results. Allele missense variant frequency (with frequency less than 0.1%) in TTN in healthy Russian population amount to 15.1 %, and truncating variants — 0.52 %. 37,9 % of them were variants of unknown significance, 62 % — likely-benign and 0.1 % — benign. There was no pathological and likely-pathological variants. Identified genetic variants distributed throughout the titin structure.Conclusion. Received result is congruent с international data bases and researches. Expended laboratory method (Next generation sequencing and confirmation with Sanger sequencing) can be used both in clinical practice, and in creating data bases of genetic variants in healthy Russian population.

scholarly journals Clinical results and importance of next-generation sequencing (NGS) in detecting targeted mutations in the treatment of metastatic Lung Cancer: Single center initial results

2019 ◽  
Vol 6 (12) ◽  
pp. 327-332
Author(s):  
Cem Mirili ◽  
Çiğdem Kahraman ◽  
Ali Yılmaz ◽  
Mehmet Bilici ◽  
Salim Başol Tekin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Genetic Variant ◽  
Clinical Results ◽  
Clinical Effects ◽  
Next Generation ◽  
Variant Analysis ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Objective:  In Lung cancer (LC), which is one of the most deadly cancers, longer survival has been achieved with targeted agents. For this reason, it is important to find the patients who are suitable for targeted therapies. Next-generation sequencing (NGS) is a method that allows multiple genetic variants to be detected simultaneously by performing massive parallel DNA sequencing at the same time. We wanted to reveal the clinical effects and benefits of genetic variant analysis with NGS for our patients. Material and Methods: Patients with stage 4 non-squamous and not otherwise specified (NOS) Non-small cell LC who underwent genetic variant analysis with NGS were included in the study, retrospectively. Results: Total of the 51 patients, 41 (80.4%) were male and the median age was 64 (35-85) years. According to TNM, 21 (41.2%) patients were stage 4A, 30 (58.8%) patients were stage 4B and 39 (76.5%) patients had adenocarcinoma and 12 (23.5%) had NOS histology. NGS analyzes were performed in median 14 days (8-43) and determined 24 pathogenic variants in 17 (%25) patients: 9EGFR (%17,6), 6PIKC3A (%11,7), 5KRAS (%9,8), 2PTEN (%3,9), 1BRAF (%1,9), 1MET (%1,6) (7 of them concomitantly). Cytotoxic chemotherapy was recommended in 41, anti-EGFR agents in 8 (afatinib in 4, erlotinib in 4 patients) patients and anti-BRAF+MEK inhibitor agent (dabrafenib+trametinib) in 1 patient. Conclusion: With the NGS, in just two weeks, both target and resistance genetic variants of our patients were detected at the same time and individualized treatments were applied. In this way, both time and cost were saved.

Performance of next-generation sequencing for detection of clinically actionable genetic variants in cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11099-11099
Author(s):  
Mohammed Omar Hussaini ◽  
Ian S. Hagemann ◽  
Teresa Mary Cox ◽  
Christina Lockwood ◽  
Karen Seibert ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Simultaneous Detection ◽  
Genetic Alterations ◽  
Sequence Variants ◽  
Tumor Type ◽  
Cancer Genes ◽  
Next Generation ◽  
Therapeutic Implications ◽  
Generation Sequencing

11099 Background: Next-generation sequencing (NGS) allows for simultaneous detection of numerous actionable somatic variants in cancer. We have implemented a clinical NGS panel to detect genetic alterations in 25 genes with established roles in cancer and report here the frequency of clinically actionable genetic variants in a variety of cancer types. Methods: NGS testing was performed in a CAP-certified, CLIA-licensed environment on DNA extracted from FFPE tissue in 209 cases spanning 41 histologic tumor types. DNA was enriched by hybrid capture and sequenced to >1,000x average coverage on Illumina sequencers with 2x101bp or 2x150bp reads. Variants were called using clinically validated parameters using the Genome Analysis Toolkit, Pindel, and the custom-written Clinical Genomicist Workstation. Results: Non-small cell lung cancer (45%), pancreatic cancer (10%), and colorectal cancer (8%) were the most common tumors sent for NGS analysis. An average of 3 (range 1- 16) non-synonymous, non-SNP sequence variants per case (SNVs and indels) were detected in the 130kb exonic target. Variants were most commonly seen in TP53, KRAS, and EGFR. 27% of cases (56/209) had one or more variants with therapeutic implications for the tumor type tested (e.g., EGFR mutation in NSCLC). 15% of cases (32/209) showed actionable variants not generally associated with the malignancy tested (e.g., detection of an activating KITvariant in thymic carcinoma). 10% of cases (21/209) had variants that were prognostically significant but not directly targetable. Some cases (9%) had variants that were prognostic/diagnostic and targetable. In 117 cases (56% of total), no therapeutically or prognostically significant variants were identified. Overall, in 92 cases (44%), NGS testing yielded information with therapeutic (majority), prognostic, or diagnostic ramifications. Conclusions: We found that 44% of unselected cancer cases have clinically relevant sequence variants in a set of 25 commonly mutated cancer genes. Our data suggest that clinical NGS testing may serve as an integral tool in realizing the potential of precision medicine in oncology.

scholarly journals NOVEL CYP2C19 GENETIC VARIANTS ASSOCIATED WITH STENT THROMBOSIS: A NEXT GENERATION SEQUENCING STUDY

2018 ◽  
Vol 71 (11) ◽  
pp. A1205
Author(s):  
Kashish Goel ◽  
Saurabh Baheti ◽  
Axel Åkerblom ◽  
Niclas Eriksson ◽  
Lars Wallentin ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Stent Thrombosis ◽  
Genetic Variants ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Targeted Next-Generation Sequencing Identifies ABCA4 Mutations in Chinese Families with Childhood-Onset and Adult-Onset Stargardt Disease

2021 ◽  
Author(s):  
Ling-hui Qu ◽  
Xin Jin ◽  
Chao Zeng ◽  
Nian-gou Zhou ◽  
Yan-hong Liu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Chinese Patients ◽  
Macular Dystrophy ◽  
Adult Onset ◽  
Next Generation ◽  
Childhood Onset ◽  
Stargardt Disease ◽  
Chinese Families ◽  
Generation Sequencing

Background: Stargardt disease (STGD) is the most common form of juvenile macular dystrophy associated with progressive central vision loss, and is agenetically and clinically heterogeneous disease. Molecular diagnosis is of great significance in aiding the clinical diagnosis, helping to determine the phenotypic severity and visual prognosis. In this study, we determined the clinical and genetic features of seven childhood-onset and three adult-onset Chinese STGD families. We performed capture next generation sequencing (NGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes.  Methods: In all, 10unrelated Chinese families were enrolled. Panel based NGS was performed to identify potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes, including the five known STGD genes (ABCA4, PROM1, PRPH2, VMD2 and ELOVL4). Variant analysis, Sanger validation, and segregation tests were utilized to validate the disease-causing mutations inthese families. Results: Using systematic data analysis with an established bioinformatics pipeline and segregation analysis, 17 pathogenic mutations in ABCA4 were identified in the ten STGD families. Four of these mutations were novel: c.371delG, c.681T > G, c.5509C > T and EX37del. Childhood-onset STGD was associated with severe visual loss, generalized retinal dysfunction and was due to more severe variants in ABCA4 than those found in adult-onset disease. Conclusions: We expand the existing spectrum of STGD and reveal the genotype-phenotype relationships of the ABCA4 mutations in Chinese patients. Childhood-onset STGD lies at the severe end of the spectrum of ABCA4-associated retinal phenotypes.

scholarly journals Molecular profiling of congenital glioblastoma using a next-generation sequencing panel

2021 ◽  
Author(s):  
Débora Cabral de Carvalho Corrêa ◽  
Francine Tesser-Gamba ◽  
Nasjla da Silva ◽  
Andrea Capellano ◽  
Maria Teresa Alves ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Next Generation ◽  
Congenital Brain Tumor ◽  
Molecular Alterations ◽  
Pathogenic Variants ◽  
Pediatric Neoplasms ◽  
Tumor Entity ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Background Congenital GBM (cGBM), presenting prenatally or within the first months of life, is among the rarest type of congenital brain tumor, with approximately 120 cases reported. Due to its infrequent occurrence, few studies have focused on the molecular and genetic aspects of this tumor, and the mutational events involved in the pathogenesis and progression of cGBM still remains poorly understood. This study aimed to investigate molecular alterations, with a potential prognostic marker and therapeutic target in cGBM using the next-generation sequencing (NGS) strategy. Methods We selected seven tumor samples from patients diagnosed with cGBM and treated at Pediatric Oncology Institute-GRAACC/UNIFESP. NGS was performed to identify somatic genetic variants in tumor samples using the Oncomine Childhood Cancer Research Assay panel, from ThermoFisher Scientific, designed specifically for pediatric neoplasms. Results Of all seven patients analyzed, three patients exhibited tumors with genetic variants, which include two pathogenic variants in NF1 and SUZ12 genes that have not been reported in cGBM yet, an increase in the number of copies of ALK gene, and two gene fusions, PPP1CB-ALK and TPM3-NTRK1. Also, none of the cases showed variants in H3F3A, TP53 and ATRX genes, alterations which are frequently seen in pediatric and adolescent GBM. Conclusions Our results suggest that cGBM may comprise a unique tumor entity and alterations in ALK and NTRK genes provide a potential target for therapy. Therefore, identification of genetic variants in cGBM is highly relevant in order to define prognosis and therapeutic strategies.

Molecular profiling of pediatric and adolescent ependymomas: identification of genetic variants using a next-generation sequencing panel

2021 ◽  
Author(s):  
Débora Cabral de Carvalho Corrêa ◽  
Francine Tesser-Gamba ◽  
Indhira Dias Oliveira ◽  
Nasjla Saba da Silva ◽  
Andrea Maria Capellano ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Molecular Profiling ◽  
Next Generation ◽  
Generation Sequencing
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