59. Oncogenic assessment of FLT3 variants by the ClinGen FLT3 Somatic Cancer Variant Curation Expert Panel
FMS-like tyrosine kinase 3 (FLT3) variants are the most frequent alterations observed in ∼30% of acute myeloid leukemia (AML) patients. Identification of FLT3 mutations predicts patients' outcome and guides therapy using FDA-approved FLT3 inhibitors. Routine screening in AML patients at baseline and relapse for both FLT3 internal tandem duplications (ITD) and tyrosine kinase domain (T KD) mutations is recommended by the 2022 European LeukemiaNet recommendations. Unlike ITD mutations, the curation, interpretation, and reporting of various FLT3 sequence variants among molecular pathologists in the clinical diagnostic setti...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Jason Saliba, Coumarane Mani, Nathan Kopp, Nikita Mehta, Shivani Golem, Madina Sukhanova, Paulo Campregher, Yuwen Li, Destiney Allen, Wenying Zhang, Jianhua Zhao, Xiaonan Zhao, Kristin Deeb, Jie Liu, Madhu M Ouseph, Arpad Danos, Heather E Williams, Xiangq Source Type: research
60. Feasibility, accuracy and usability analysis of MapAML, a first-in-class app for integrated diagnosis in AML
Performing a comprehensive diagnosis in acute myeloid leukemia (AML) is complex and involves the integration of clinical information, bone marrow morphology, immunophenotyping, cytogenetic and molecular analysis, what can be challenging to the general hematologist. The aim of this study was to evaluate the usability and accuracy of MapAML, a smartphone app for integrated diagnosis in AML, created to aid the hematologist in its clinical practice. After input of clinical and laboratorial information, MapAML yields a report with the following items: a) WHO classification; b) European LeukemiaNet risk stratification, c) Target...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Paulo Campregher, Tha ís Moyen, Victoria Tomaz Source Type: research
61. A cell-free DNA 5-hydroxymethylcytosine marker predicts immunotherapy response in lung cancer
Novel predictive markers facilitate effective lung cancer treatment. Immune checkpoint inhibitors (ICIs) can drastically improve outcomes for lung cancer patients. However, currently no markers can accurately predict which patients will benefit from ICI therapies. We performed a genome-wide analysis of 5-hydroxymethylcytosine (5hmC) in 71 plasma cell-free DNA (cfDNA) samples from lung cancer patients. Using machine learning approaches, we developed a 5hmC signature for ICI treatment prediction in lung cancer in a training set and validated it in a validation set. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Zejuan Li, Jianming Shao, Randall Olsen, Saro Kasparian, Chuan He, Eric Bernicker Source Type: research
62. Profiling PIK3CA variants - a highlight of C2 domain variants in Disorders of Somatic Mosaicism
Somatic activating variants in PIK3CA are associated with segmental overgrowth disorders, now collectively termed PIK3CA related overgrowth spectrum (PROS). Here we analyze the genetic findings in a cohort of patients with disorders of somatic mosaicism (DoSM) and review the clinically significant PIK3CA variants with a focus on non-hotspot variants.A total of 1,232 patients with DoSM were referred for clinical next-generation sequencing (NGS) gene panel testing between 2013 and 2022. A high depth of coverage NGS analysis was performed following target enrichment using oligonucleotide-based targeted capture of exonic regio...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Yang Cao, Patricia Hernandez, Meagan Corliss, Molly Schroeder, Kevin Bowling, Kilannin Krysiak, Jonathan Heusel, Julie Neidich, Bahareh AdhamiMojarad Source Type: research
63. A female-specific chimeric RNA with differential expression in COVID patients
Clinical statistics show that women and men act differently in various diseases. In the recent coronavirus disease 2019 (COVID-19) pandemic, scientists reported that men suffered more severe symptoms and higher mortality than women. Chimeric RNA, as a new layer of RNA diversification, is defined as a hybrid transcript containing exons from two originally separate genes. To understand the fundament of sex-biased COVID-19 phenotypes, we aim to discover sex-specific chimeric RNAs and their potential functions. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Xinrui Shi, Peng Wu, Hui Li Source Type: research
64. Utilizing rapid molecular testing to reduce disparities in pediatric cancer in Sub-Saharan Africa
Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries, but precise diagnosis and successful treatment in low-resourced settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA). The goal of this study was to develop rapid molecular assays to improve pediatric cancer diagnoses in low-resourced settings. The NanoString nCounter platform was chosen due to minimal technical expertise required, ability to test sub-optimal RNA, and turn-around-time (2-3...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Julie Gastier-Foster, Faith Hollingsworth, Dolores Lopez-Terrada, Kevin Fisher, Anshumoy Roy, Peter Wasswa, Nmazuo Ozuah, Parth Mehta, Jospeh Lubega, Carl Allen, David Poplack, Fredrick Lutwama Source Type: research
65. Insights into the genetic heterogeneity of glioblastoma: gene amplification in ecDNA and HSR
Glioblastoma is a highly aggressive brain tumor characterized by genetic heterogeneity and a poor prognosis. Novel mechanisms of gene amplification occur most frequently in glioblastoma, involving extrachromosomal DNA (ecDNA) and homogeneously staining regions (HSR), compared to other human tumor types. ecDNA and HSR are circular DNA fragments and chromosomal regions that contain multiple copies of a particular oncogene, respectively. These genetic abnormal structures are thought to facilitate rapid and extensive gene amplification, leading to the upregulation of oncogenes that promote tumor growth and survival. (Source: C...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: In és Martín Barrio, Bo Zhao, Lingqun Ye, Xiaojun Liu, Peter Huc Awdhesh Kalia, Yonathan Lissanu, Manjunath Nimmakayalu, Kadir Akdemir Source Type: research
66. Screening for genetic predisposition to pediatric leukemia in a Peruvian population
Genetic predisposition to pediatric leukemias is variable among populations. Pathogenic/likely pathogenic (P/LP) variants increase the risk of developing hematologic malignancies that can be identified by massive sequencing (NGS). Peru has one of the highest incidence and mortality rates for pediatric leukemia in Latin America. Our aim was to determine the frequency of genetic predisposition to pediatric leukemia in the Peruvian population. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Jeny Bazalar-Montoya, Richard S. Rodriguez, Francisco Sanchez-Pinto, Julissa Fuentes-Vera, Guillermo Romero-Guerra, Monica Correa-Guerrero, Ricardo Abanto-Hinostroza, Sergio Murillo-Vizcarra, Victoria Godoy-Vila, Gioconda Manassero-Morales Source Type: research
67. Target capture NGS for use in molecular-based research of myeloid measurable residual disease
Molecular technologies incorporating NGS are increasingly utilised to support traditional immunophenotypic multiparameter flow cytometry in MRD detection, including acute myeloid leukaemia (AML) disease monitoring.We used the OGTTM Universal NGS Complete Workflow Solution library preparation kit and a focussed SureSeqTM Myeloid MRD panel to assess the applicability of a capture-based target enrichment NGS approach for studies of molecular-based MRD monitoring in AML. The panel covers 43 hotspot exons in 13 genes relevant to the AML panel (11.3 kb baited, 8 kb targeted). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Rebecca Biloune Source Type: research
68. Orthogonal approaches to validate a knowledgebase of interpretations of clinically relevant somatic cancer variants
The interpretation of genomic data by clinical laboratory professionals remains a bottleneck in precision oncology. We applied several approaches to analyze the comprehensiveness and accuracy of variant classification and clinical impact assertions of Velsera's Knowledgebase (KB), an automated solution to interpret somatic mutations in cancer.A panel of four independent pathologists reviewed the accuracy of variant interpretations, classification on the AMP/ASCO/CAP scheme, clinical impact associations, and clinical trial matching. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Andrew Bredemeyer, Gargi Nanda, Anuja Jedhe, Aditi Phatak, Nikita Deshmukh, Vidya Iyer, Rhucha Vatturkar, Sukanya Sengupta, Pamela Hesker, Rakesh Nagarajan Source Type: research
69. Efficient clinical review of complex NGS tumor copy number profiles using ACMG/CGC guidelines and an interactive web app
Clinical analysis and reporting of somatically acquired copy number abnormalities (CNAs) detected through genome-wide next-generation sequencing (NGS) is time consuming and requires significant expertise. Recent guidelines for the clinical assessment of tumor CNAs harmonized and simplified the reporting criteria but did not directly address NGS-specific concerns or the need for a standardized and scalable analysis protocol. Therefore, a Standard Operating Procedure (SOP) for CNA analysis is needed to address these challenges and provide opportunities for efficient clinical review and reporting. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Ellen Chen, Jinlian Wang, Robert Kueffner, Hussam Al-Kateb, Antonina Silkov, Andrew Uzilov, Lucas Lochovsky, Hui Li, Scott Newman Source Type: research
70. Epigenetic reprogramming in thalamic H3K27-altered glioma neural progenitor cells
H3K27-altered diffuse midline gliomas (DMGs) are devastating cancers occurring mainly in young children in the thalamus and brainstem, characterized by a mutation which inhibits the polycomb repressive complex 2 (PRC2) and the resultant widespread loss of the repressive histone modification H3K27me3. H3K27me3 is essential for lineage differentiation. We assembled a single cell dataset from the normal human prenatal and young adult thalamus to better understand the precise regional and developmental origins of these thalamic tumors. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Allison Cheney, Yuanqing (Bianca) Xue, A. Geoffrey Lyle, Ellen T. Kephart, Josh M. Stuart, Olena M. Vaske Source Type: research
71. Integrated genomic analysis of hepatocellular carcinoma using WES and aCGH
A retrospective study was conducted on a case series of hepatocellular carcinoma (HCC) using whole exome sequencing (WES) and array comparative genomic hybridization (aCGH) to evaluate genetic defects for underlying mechanisms and clinicopathologic associations. Paired DNA samples from tumor and adjacent nontumor tissues of 36 HCC cases and their clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status were collected. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Mei Ling Chong, Hongyan Chai, Qiping Hu, Peining Li Source Type: research
72. Comprehensive genomic profiling in the diagnosis of Central Nervous System tumors
The inclusion of molecular biomarkers to traditional histological diagnoses has resulted in significant changes in the World Health Organization (WHO) classification of central nervous system (CNS) tumors. The current study aims to demonstrate the importance of genomic profiling analysis for CNS tumor classification based on clinical laboratory experience. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Luiz Gustavo Ferreira Cortes, Caroline Nunes Silveira, Larissa Barbosa de Lima, Karla de Oliveira Pelegrino, Vitor Ribeiro Paes, Paulo Vidal Campregher Source Type: research
73. Optimization and clinical validation of the Ion Torrent Oncomine comprehensive assay plus
The Oncomine Comprehensive Assay Plus v3, (OCAPlus, ThermoFisher) provides an in-house comprehensive genomic profiling solution appropriate for formalin-fixed, paraffin-embedded (FFPE) tissues. The assay uses matched DNA and RNA (cDNA) to detect single nucleotide variants (SNVs) and small deletions and insertions (DELINS) in over 500 genes, copy number variants (CNVs) in over 300 genes, gene fusions (SVs) in 49 genes, tumor mutational burden (TMB), and microsatellite stability (MSI). Validation consisted of 100 clinical samples representing 8 different cancer types, 6 synthetic controls, and 2 cell lines. (Source: Cancer G...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Jennifer Crow, Stephen Hyter, Sarah Schmitt, Andrew Godwin Source Type: research
