scholarly journals Congress of Neurological Surgeons Systematic Review and Evidence-based Guidelines Update on the Role of Neuropathology in the Management of Progressive Glioblastoma in Adults

2022 ◽  
Author(s):  
Abigail Goodman ◽  
José E. Velázquez Vega ◽  
Chad Glenn ◽  
Jeffrey J. Olson
Keyword(s):  
Promoter Methylation ◽  
Mutation Testing ◽  
Adult Patients ◽  
Initial Presentation ◽  
Whole Genome ◽  
Prognostic Information ◽  
Repeat Testing ◽  
Histologic Analysis ◽  
Large Panel ◽  
Panel Sequencing

Abstract Target population These recommendations apply to adult patients with progressive or recurrent glioblastoma (GBM).QuestionFor adult patients with progressive glioblastoma does testing for Isocitrate Dehydrogenase (IDH) 1 or 2 mutations provide new additional management or prognostic information beyond that derived from the tumor at initial presentation?RecommendationLevel III: Repeat IDH mutation testing is not necessary if the tumor is histologically similar to the primary tumor and the patient’s clinical course is as expected. Question For adult patients with progressive glioblastoma does repeat testing for MGMT promoter methylation provide new or additional management or prognostic information beyond that derived from the tumor at initial presentation and what methods of detection are optimal?Recommendation Level III: Repeat MGMT promoter methylation is not recommended. Question For adult patients with progressive glioblastoma does EGFR amplification or mutation testing provide management or prognostic information beyond that provided by histologic analysis and if performed on previous tissue samples, does it need to be repeated?RecommendationLevel III: In cases that are difficult to classify as glioblastoma on histologic features EGFR amplification testing may help in classification. If a previous EGFR amplification was detected, repeat testing is not necessary. Repeat EGFR amplification or mutational testing may be recommended in patients in which target therapy is being considered.Question For adult patients with progressive glioblastoma does whole genome or large panel sequencing provide management or prognostic information beyond that derived from histologic analysis?RecommendationLevel III: Primary or repeat whole genome or large panel sequencing may be considered in patients who are eligible or interested in molecularly guided therapy or clinical trials.QuestionFor adult patients with progressive glioblastoma should immune checkpoint biomarker testing be performed to provide management and prognostic information beyond that obtained from histologic analysis?RecommendationLevel III: The current evidence does not support making PD-L1 or mismatch repair (MMR) enzyme activity a component of standard testing.QuestionFor adult patients with progressive glioblastoma are there meaningful biomarkers for bevacizumab responsiveness and does their assessment provide additional information for tumor management and prognosis beyond that learned by standard histologic analysis?RecommendationLevel III: No established Bevacizumab biomarkers are currently available based upon the inclusion criteria of this guideline.

scholarly journals Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity

2019 ◽  
Vol 11 (1) ◽  
pp. e289
Author(s):  
P. Richard ◽  
F. Ader ◽  
M. Roux ◽  
Erwan Donal ◽  
Jean-Christophe Eicher ◽  
...  
Keyword(s):  
Genetic Heterogeneity ◽  
Left Ventricular ◽  
Adult Patients ◽  
Panel Sequencing

scholarly journals D-GPM: A Deep Learning Method for Gene Promoter Methylation Inference

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 807 ◽  
Author(s):  
Pan ◽  
Liu ◽  
Wen ◽  
Liu ◽  
Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Deep Learning ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Gene Promoter ◽  
Support Vector ◽  
Whole Genome ◽  
Expression Levels ◽  
Gene Expression Levels

Whole-genome bisulfite sequencing generates a comprehensive profiling of the gene methylation levels, but is limited by a high cost. Recent studies have partitioned the genes into landmark genes and target genes and suggested that the landmark gene expression levels capture adequate information to reconstruct the target gene expression levels. This inspired us to propose that the methylation level of the promoters in landmark genes might be adequate to reconstruct the promoter methylation level of target genes, which would eventually reduce the cost of promoter methylation profiling. Here, we propose a deep learning model called Deep-Gene Promoter Methylation (D-GPM) to predict the whole-genome promoter methylation level based on the promoter methylation profile of the landmark genes from The Cancer Genome Atlas (TCGA). D-GPM-15%-7000 × 5, the optimal architecture of D-GPM, acquires the least overall mean absolute error (MAE) and the highest overall Pearson correlation coefficient (PCC), with values of 0.0329 and 0.8186, respectively, when testing data. Additionally, the D-GPM outperforms the regression tree (RT), linear regression (LR), and the support vector machine (SVM) in 95.66%, 92.65%, and 85.49% of the target genes by virtue of its relatively lower MAE and in 98.25%, 91.00%, and 81.56% of the target genes based on its relatively higher PCC, respectively. More importantly, the D-GPM predominates in predicting 79.86% and 78.34% of the target genes according to the model distribution of the least MAE and the highest PCC, respectively.

scholarly journals Prediction of mortality in adult patients with sepsis using six biomarkers: a systematic review and meta-analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Andreas Pregernig ◽  
Mattia Müller ◽  
Ulrike Held ◽  
Beatrice Beck-Schimmer
Keyword(s):  
Systematic Review ◽  
Literature Search ◽  
Meta Analysis ◽  
Advanced Glycation Endproducts ◽  
Adult Patients ◽  
Cochrane Library ◽  
Systematic Literature Search ◽  
Prognostic Information ◽  
Prediction Of Mortality ◽  
Mean Differences

Abstract Background Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor expressed on myeloid cells 1 (sTREM1), and soluble urokinase-type plasminogen activator receptor (suPAR) have shown promising results for predicting all-cause mortality in critical care patients. The aim of our systematic review and meta-analysis was to assess the prognostic value of these biomarkers for mortality in adult patients with sepsis. Methods A systematic literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases, for articles in English published from 01.01.1990 onwards, was conducted. The systematic review focused exclusively on observational studies of adult patients with sepsis, any randomized trials were excluded. For the meta-analysis, only studies which provide biomarker concentrations within 24 h of admission in sepsis survivors and nonsurvivors were included. Results are presented as pooled mean differences (MD) between nonsurvivors and survivors with 95% confidence interval for each of the six biomarkers. Studies not included in the quantitative analysis were narratively summarized. The risk of bias was assessed in all included studies using the Quality in Prognosis Studies (QUIPS) tool. Results The systematic literature search retrieved 2285 articles. In total, we included 44 studies in the qualitative analysis, of which 28 were included in the meta-analysis. The pooled mean differences in biomarker concentration (nonsurvivors − survivors), measured at onset of sepsis, are listed as follows: (1) Ang-1: − 2.9 ng/ml (95% CI − 4.1 to − 1.7, p < 0.01); (2) Ang-2: 4.9 ng/ml (95% CI 2.6 to 7.1, p < 0.01); (3) HMGB1: 1.2 ng/ml (95% CI 0.0 to 2.4, p = 0.05); (4) sRAGE: 1003 pg/ml (95% CI 628 to 1377, p < 0.01); (5) sTREM-1: 87 pg/ml (95% CI 2 to 171, p = 0.04); (6) suPAR: 5.2 ng/ml (95% CI 4.5 to 6.0, p < 0.01). Conclusions Ang-1, Ang-2, and suPAR provide beneficial prognostic information about mortality in adult patients with sepsis. The further development of standardized assays and the assessment of their performance when included in panels with other biomarkers may be recommended. Trial registration This study was recorded on PROSPERO, prospective register of systematic reviews, under the registration ID: CRD42018081226

scholarly journals Targeted panel sequencing in adult patients with left ventricular non‐compaction reveals a large genetic heterogeneity

2018 ◽  
Vol 95 (3) ◽  
pp. 356-367 ◽  
Author(s):  
Pascale Richard ◽  
Flavie Ader ◽  
Maguelonne Roux ◽  
Erwan Donal ◽  
Jean‐Christophe Eicher ◽  
...  
Keyword(s):  
Genetic Heterogeneity ◽  
Left Ventricular ◽  
Adult Patients ◽  
Panel Sequencing

Review of 200 consecutive patients with mutation profiling in a lung cancer individualized medicine clinic.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19013-e19013
Author(s):  
Michael Asiedu ◽  
Julian R. Molina ◽  
Jin Jen ◽  
Jin Sung Jang ◽  
Anja Roden ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Individualized Medicine ◽  
Treatment Decisions ◽  
Mutation Testing ◽  
Egfr Mutations ◽  
Driver Gene ◽  
Whole Genome ◽  
Number Of Patients ◽  
Mutation Profiling

e19013 Background: Mutation profiling to assess for potentially druggable mutations in NSCLC is being offered at an increasing number of cancer centers throughout North America and internationally. Although data continue to accumulate for the potential value of mutation testing in designing chemotherapeutic regimens, the treatment impact of obtaining information beyond assessment of EGFR and ALK status remains unclear. How best to obtain and clinically utilize these data, including information from exome and whole genome sequencing, also remains unclear. Methods: Patients were reviewed electronically in a multidisciplinary conference regarding indications for testing and results of mutation profiling from various methods, including the mass-spec based LungCarta test, targeted NexGen sequencing, exome, and whole genome sequencing. Outcomes of the multidisciplinary review were communicated back to treating physicians. Results: Mutation testing was performed on 200 patients using a variety of approaches. The majority (>150) were surgically resected stage I and II tumors. Mutations in at least 1 major cancer driver gene, including EGFR, KRAS, MET, BRAF and PIK3CA, were found in 47% of all patients tested. EGFR mutations were present in 14.8% of patients tested, KRAS 21.3%, BRAF 2.6%, PIK3CA 3.2%, and MET 4.5%. A total of 8 patients underwent either exome or whole genome sequencing. A limited number of patients (<10) had mutation results that impacted treatment decisions from this cohort. Conclusions: Mutation profiling can influence treatment decisions in NSCLC, but at a low frequency. The role of exome and or whole genome sequencing for patients with NSCLC is evolving and remains undefined.

scholarly journals Whole genome scanning as a cytogenetic tool in hematologic malignancies

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 965-974 ◽  
Author(s):  
Jaroslaw P. Maciejewski ◽  
Ghulam J. Mufti
Keyword(s):  
Neutral Loss ◽  
Uniparental Disomy ◽  
Hematologic Malignancies ◽  
Comparative Genomic ◽  
Whole Genome ◽  
Prognostic Information ◽  
Therapeutic Modalities ◽  
Genome Scanning ◽  
Balanced Translocations ◽  
Chromosomal Defects

Abstract Over the years, methods of cytogenetic analysis evolved and became part of routine laboratory testing, providing valuable diagnostic and prognostic information in hematologic disorders. Karyotypic aberrations contribute to the understanding of the molecular pathogenesis of disease and thereby to rational application of therapeutic modalities. Most of the progress in this field stems from the application of metaphase cytogenetics (MC), but recently, novel molecular technologies have been introduced that complement MC and overcome many of the limitations of traditional cytogenetics, including a need for cell culture. Whole genome scanning using comparative genomic hybridization and single nucleotide polymorphism arrays (CGH-A; SNP-A) can be used for analysis of somatic or clonal unbalanced chromosomal defects. In SNP-A, the combination of copy number detection and genotyping enables diagnosis of copy-neutral loss of heterozygosity, a lesion that cannot be detected using MC but may have important pathogenetic implications. Overall, whole genome scanning arrays, despite the drawback of an inability to detect balanced translocations, allow for discovery of chromosomal defects in a higher proportion of patients with hematologic malignancies. Newly detected chromosomal aberrations, including somatic uniparental disomy, may lead to more precise prognostic schemes in many diseases.

scholarly journals Workflow optimization of whole genome amplification and targeted panel sequencing for CTC mutation detection

2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Haiyan E. Liu ◽  
Melanie Triboulet ◽  
Amin Zia ◽  
Meghah Vuppalapaty ◽  
Evelyn Kidess-Sigal ◽  
...  
Keyword(s):  
Whole Genome Amplification ◽  
Mutation Detection ◽  
Whole Genome ◽  
Genome Amplification ◽  
Workflow Optimization ◽  
Panel Sequencing
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