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

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.

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

Medical Science and Discovery ◽

10.36472/msd.v6i12.330 ◽

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.

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Molecular profiling of osteosarcoma in children and adolescents from different age groups using a next-generation sequencing panel

Cancer Genetics ◽

10.1016/j.cancergen.2021.10.002 ◽

2021 ◽

Author(s):

G.M. Guimarães ◽

F. Tesser-Gamba ◽

A.S. Petrilli ◽

C.R.P. Donato-Macedo ◽

M.T.S. Alves ◽

...

Keyword(s):

Next Generation Sequencing ◽

Children And Adolescents ◽

Age Groups ◽

Molecular Profiling ◽

Next Generation ◽

Generation Sequencing

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Abstract P2-08-13: Integrating multiplex and next generation sequencing (NGS) platforms in routine molecular profiling of metastatic breast cancer (MBC) patients (pts): Trends for enrollment in genotype-directed clinical trials (GDTs)

10.1158/1538-7445.sabcs15-p2-08-13 ◽

2016 ◽

Author(s):

M Oliveira ◽

R Dienstmann ◽

M Bellet ◽

JM Pérez-Garcia ◽

P Gómez ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Metastatic Breast Cancer ◽

Next Generation Sequencing ◽

Metastatic Breast ◽

Molecular Profiling ◽

Next Generation ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11099 ◽

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.

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Molecular profiling of lung adenocarcinoma using pleural effusion specimens.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21709 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21709-e21709

Author(s):

Wei Zhang ◽

Bei Zhang ◽

Yifan Zhou ◽

Xiaochen Zhao ◽

Yuezong Bai

Keyword(s):

Targeted Therapy ◽

Next Generation Sequencing ◽

Pleural Effusion ◽

Lung Adenocarcinoma ◽

Copy Number ◽

Copy Number Gain ◽

Molecular Profiling ◽

Copy Number Loss ◽

Next Generation ◽

Generation Sequencing

e21709 Background: Molecular profiling of lung adenocarcinoma is essential for therapeutic decision-making and prognosis predicting. Pleural effusion may provide an opportunity for molecular profiling and thereby possibly provide information enabling targeted therapy. In this study, we performed next generation sequencing (NGS) in pleural effusion samples in order to study molecular profiling of lung adenocarcinoma using pleural effusion specimens. Methods: 45 Chinese lung adenocarcinoma patients with pleural effusion specimens were included. The pleural effusion samples were centrifugated, then cell pellets were collected and prepared into cell blocks. Genetic mutations were assessed using a validated targeted next generation sequencing assay. Immunohistochemistry (IHC) of PD-L1 was performed with 22C3 kit. Results: In 45 pleural effusion samples collected, 43 (95.5%) patients had at least one mutation classed as pathogenic or likely pathogenic. There were 245 somatic mutation and 160 germline mutations were detected, with an average of 8.0 mutations per patient. Of the 45 specimens with somatic mutations, seventeen (37.8%) of harbored EGFR mutations. The most frequent mutations were the deletion mutation in exon19 (15/17, 40.9%), the point mutation (L858R) in exon 21 (13/17, 76.5%), and resistance mutation (T790M) in exon 20(4/17,23.5%). Aside from the EGFR mutation, 1 case exhibited KRAS mutation (G12C), 1 case harbored ERBB2 mutation(Y772_A775dup),1 case harbored TP53 mutation, and 2 cases exhibited fusion (EML4-ALK, KIF5B-RET). 2 cases exhibited CD274 copy number gain, 2 cases exhibited CDK4 copy number gains, and one case carried CDK6 copy number gain, one case carried CKD6 copy number loss. The top frequent germline mutation genes were APC (5/45), ALK (4/45), ARID1A (4/45) and BARD1 (4/45). Regarding biomarkers for immunotherapy, three sample showed TMB-H (6.7%), and one sample showed MSI-H (2.2%). Of 29 samples underwent PDL1 IHC test, 21 samples (72.4%) show positive PDL1 expression, in concordance with previous reported rates. Conclusions: These results suggest that pleural effusions are important specimens for oncogene mutation analysis and enable targeted therapy for patients with lung adenocarcinoma.

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