Faculty Opinions recommendation of High Prevalence of DICER1 Mutations and Low Frequency of Gene Fusions in Pediatric Follicular-Patterned Tumors of the Thyroid.

2021 ◽  
Author(s):  
Virginia LiVolsi
Keyword(s):  
Low Frequency ◽  
Gene Fusions ◽  
High Prevalence

High Prevalence of DICER1 Mutations and Low Frequency of Gene Fusions in Pediatric Follicular-Patterned Tumors of the Thyroid

2021 ◽  
Author(s):  
Ja-Seong Bae ◽  
Seung-Hyun Jung ◽  
Mitsuyoshi Hirokawa ◽  
Andrey Bychkov ◽  
Akira Miyauchi ◽  
...  
Keyword(s):  
Low Frequency ◽  
Gene Fusions ◽  
High Prevalence

Detecting ultra low-frequency variants and gene fusions in lung cancer patients using an amplicon-based Firefly NGS method.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23062-e23062
Author(s):  
Li Weng ◽  
Lin Wang ◽  
Xiao Chen ◽  
Jacey Zhang ◽  
Chiahui Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Cancer Patients ◽  
Allele Frequency ◽  
Sensitivity And Specificity ◽  
Low Frequency ◽  
Analytical Sensitivity ◽  
Gene Fusions ◽  
Lung Cancer Patients

e23062 Background: The analysis of EGFR, KRAS, and BRAF mutations and Alk fusion is critical for guiding targeted therapy selection, detecting drug resistance, and monitoring residual disease in patients with NSCLC. Designing next-generation sequencing (NGS) assays for detecting low-frequency variants, however, is an ongoing challenge. The limited availability of cfDNA combined with the breadth of coverage necessary to create meaningful, clinically-actionable results requires a solution with multiplex capacity which, in turn, requires greater technological sensitivity and specificity. Here we aim to develop such a solution: an ultra-accurate NGS technology using concatmer-based error correction with amplicon workflow for fast detection of rare mutations including SNV and fusion. Methods: We developed an amplicon-based panel covering variants of EGFR, BRAF, and KRAS, as well as a panel to detect Alk fusion. CfDNA simulate and cfDNA from healthy individuals were used to test assay sensitivity and specificity. Further validation was performed via a comparative analysis of 64 late-stage lung cancer patients using both Firefly -Comet and ddPCR. Results: Analytical sensitivity of the EGFR-TKI 3-gene panel was 100% detection at an allele frequency of 0.1% for 20ng of cfDNA input. Similarly, analytical sensitivity of the Alk fusion panel was 75% detection at an allele frequency of 0.1% and 100% at an allele frequency of 0.25% for the same input. Among our patient cohort, 5 EGFR variants (19del, T790M, L858R, G719X, L861X) and 2 KRAS variant (G12X) were detected. Firefly-Comet demonstrated strong per-variant detection-rate concordance ( > 99%) compared to ddPCR results. The PPV is 100% and the NPV is 98.7%. Statistical analysis of reported allele frequency concordance between Firefly-Comet and ddPCR reveals R-Sq > 0.9. Conclusions: In summary, we have developed Firefly-Comet, an easy-to-use amplicon-based NGS assay capable of detecting single-digit copies of somatic mutants and gene fusions in cfDNA. The multiplex capacity of Firefly-Comet makes it well-suited for supporting targeted therapy selection, drug resistance detection, and treatment monitoring.

scholarly journals Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults

2021 ◽  
Vol 28 (1) ◽  
pp. 523-548
Author(s):  
D. Gwyn Bebb ◽  
Shantanu Banerji ◽  
Normand Blais ◽  
Patrice Desmeules ◽  
Sharlene Gill ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Effective Treatment ◽  
Gene Fusion ◽  
Treatment Options ◽  
Low Frequency ◽  
Gene Fusions ◽  
Receptor Kinase ◽  
Cell Lung Carcinoma ◽  
Rare Tumours ◽  
Tyrosine Receptor Kinase

The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. These NTRK gene fusions are oncogenic drivers found in most tumour types at a low frequency (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., secretory carcinoma of the salivary gland and of the breast). They are generally mutually exclusive of other common oncogenic drivers. Larotrectinib and entrectinib have demonstrated impressive overall response rates and tolerability in Phase I/II trials in patients with TRK fusion cancer with no other effective treatment options. Given the low frequency of TRK fusion cancer and the heterogeneous molecular testing landscape in Canada, identifying and optimally managing such patients represents a new challenge. We provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor. We focus on five tumour types: thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, soft tissue sarcoma, and salivary gland carcinoma. Based on the probability of the tumour harbouring an NTRK gene fusion, we also suggest a tumour-agnostic consensus for NTRK gene fusion testing and treatment. We recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options.

Gene fusions in glioblastoma: Results of Gliocat project.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2042-2042
Author(s):  
Ainhoa Hernandez Gonzalez ◽  
Anna Esteve-Codina ◽  
Cristina Carrato ◽  
Ana Munoz ◽  
Estela Pineda ◽  
...  
Keyword(s):  
Gene Fusion ◽  
Molecular Subtype ◽  
Malignant Gliomas ◽  
Low Frequency ◽  
Large Data ◽  
Patient Specific ◽  
Gene Fusions ◽  
Rna Seq ◽  
Data Set ◽  
Novel Treatments

2042 Background: Malignant gliomas are heterogeneous diseases in genetic basis. The development of sequencing techniques, such as RNA-Sequencing, has identified many gene rearrangements encoding novel oncogenic fusions. Gene fusion discovery can potentially lead to the development of novel treatments, however studies of gene fusions in glioma remain limited. Methods: The GLIOCAT project studied 139 patient samples of newly diagnosed glioblastoma who had received the standard first-line treatment from 2004 to 2015, to identify gene fusion events from glioblastoma transcriptome data (RNA-Seq). The molecular subtype could be studied in 124 cases. RNA-Seq reads were mapped against the reference human genome with STAR-fusion version 0.7.0, specifically, with FusionInspector validate ( http://star-fusion.github.io ). Two other platforms, FusionHub ( https://fusionhub.persistent.co.in ) and Oncofuse ( www.unav.es/genetica/oncofuse.html ), were applied to eliminate false positives or previously described in healthy tissue and to predict of the oncogenic potential each fusion. Results: A total of61 patients showed 103 different fusions, a median of two fusions by sample. The majority of gene fusions were intrachromosomal and most frequently implied chromosome was 12 followed by 7. In addition, fusions were more common in patients with MGMT promoter methylation, TCGA classical subtype and 18 IGS subtype. There were no differences in age, sex, type of surgery or long survivors ( > 30 months). Ten fusions were already described in cancer, including three in gliomas (FRS2-KIF5A, EGFR-SEPT14 and FGFR3-TACC3). From the detected fusions, 22 of them included an oncogene or protooncogene. Conclusions: In our study, we report the landscape of gene fusions from a large data set of glioblastomas analyzed by RNA-seq. The majority of the fusions were private fusions. A minority of these recur in a low frequency but as many as a quarter of them included an oncogene or protooncogene. RNA-seq of GBM patient samples it is an important tool for the identification of patient-specific fusions that could drive personalized therapy. Furtherless, we will plan to validate this gene fusions.

scholarly journals Genomic characterization and outcome evaluation of kinome fusions in lung cancer revealed novel druggable fusions

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Binghao Li ◽  
Hao Qu ◽  
Jing Zhang ◽  
Weibo Pan ◽  
Meng Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Low Frequency ◽  
Stage Iv ◽  
Outcome Evaluation ◽  
Driver Mutations ◽  
Gene Fusions ◽  
Comprehensive Overview ◽  
Unique Gene

AbstractKinase fusions represent an important type of somatic alterations that promote oncogenesis and serve as diagnostic markers in lung cancer. We aimed to identify the landscape of clinically relevant kinase fusions in Chinese lung cancer and to explore rare kinase rearrangements; thus, providing valuable evidence for therapeutic decision making. We performed genomic profiling of 425 cancer-relevant genes from tumor/plasma biopsies from a total of 17,442 Chinese lung cancer patients using next generation sequencing (NGS). Patients’ clinical characteristics and treatment histories were retrospectively studied. A total of 1162 patients (6.66%; 1162/17,442) were identified as having kinase fusions, including 906 adenocarcinomas (ADCs) and 35 squamous cell carcinomas (SCCs). In ADC, 170 unique gene fusion pairs were observed, including rare kinase fusions, SLC12A2-ROS1, NCOA4-RET, and ANK3-RET. As for SCC, 15 unique gene fusions were identified, among which the most frequent were EML4-ALK and FGFR3-TACC3. Analyses of oncogenic mutations revealed a dual role for the gene fusions, CCDC6-RET and FGFR3-TACC3, in driving oncogenesis or serving as acquired resistance mechanisms to kinase inhibitors. In addition, our real-world evidence showed that patients with recurrent kinase fusions with low frequency (two occurrences) could benefit from treatment with kinase inhibitors’ off-label use. Notably, patients with stage IV ADC who had novel RORB-ALK or AFF2-RET fusions, but no other known oncogenic driver mutations, demonstrated favorable clinical outcomes on tyrosine kinase inhibitors. Our data provide a comprehensive overview of the landscape of oncogenic kinase fusions in lung cancer, which assist in recognizing potentially druggable fusions that can be translated into therapeutic applications.

scholarly journals FEATURES OF THE MECHANISMS OF TRANSMISSION OF HIV: VERBAL COMMUNICATION RESEARCH

2018 ◽  
Vol 23 (1) ◽  
pp. 23-29
Author(s):  
Andrey A. Malinovsky ◽  
V. I Kharchenko ◽  
T. P Bessarab ◽  
I. V Gerasimov ◽  
E. M Serebryakov ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Low Frequency ◽  
Metropolitan Region ◽  
Survey Study ◽  
Vulnerable Groups ◽  
Raising Awareness ◽  
High Prevalence ◽  
Potential Risks ◽  
The City

The aim of the study is to assess the features of the formation and implementation of the risks of HIV infection in the city of Moscow, taking into account the gender, type of contact, number of partners, sexual activity, information on the use of barrier protection means. To develop proposals for raising awareness of key (vulnerable) groups of the population. Materials and methods. A survey study involved 329 patients who were on the primary admission to the AIDS Moscow Municipal Center. Four groups of observation, separated by gender and HIV status, were selected. On the base of absolute values, the relative indices for each studied sigh were calculated, the errors in the representativeness of the relative indices were determined, the reliability of the differences in relative values was estimated, the probability of an error-free forecast was assumed to be equal to or greater than 95% (p ≥ 95%). Results and discussion There is established the high prevalence and significant role of anal intercourses (AIC) in the transmission of HIV infection to both men and women among the residents of the metropolitan region along with the lack of awareness of the potential risks of this form of sexual contact in the transmission of HIV infection. The low frequency of condom use by men practicing the AIC has been revealed. The preventive effect of control by women on the use of condoms by their partners has been confirmed. Conclusion As the main tasks to optimize preventive measures for HIV infection, it is necessary to consider informing key (vulnerable) population groups of the base of women's consultations and medical organizations of the dermatovenerologic profile concerning the potential danger of the AIC and the preventive value of barrier protection.

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