76. Goals, methods and challenges in a clinical validation of a NGS-based platform for the detection of constitutional CNVs
DNA microarrays are used in our institution since 2011 to evaluate copy number variants (CNVs) in both constitutional (prenatal and postnatal) and oncology applications. We are currently validating a NGS-based platform from the company OGT to replace our arrays in constitutional applications. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Fl échère Fortin, Natascia Anastasio, Sebastien Chenier Source Type: research
77. Copy number alterations are commonly seen in childhood brain tumors and may help predict survival
Brain and central nervous system tumors are the most common form of solid tumor cancers and the second most common cancer overall among children. Although advances have been made in understanding the genomics of childhood brain tumors, the role of copy number alterations (CNAs) has not been fully characterized. While genomes of childhood brain tumor patients are generally considered to be relatively stable diploid genomes, analysis of a subset of pretreatment diagnostic samples from a cohort of 84 deceased patients with a variety of brain cancer diagnoses from Washington University revealed widespread alterations, suggesti...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Sharon Freshour, Bryan Fisk, Christopher Miller, Joshua Rubin, Obi L. Griffith, Malachi Griffith Source Type: research
78. Identification of a non-productive KMT2A rearrangement in B-ALL with apparent concurrent ETV6::RUNX1 and KMT2A fusions
We describe a three-year-old female presenting with de novo B-ALL in whom dual color, dual fusion fluorescence in situ hybridization (D-FISH) evaluation suggested concurrent ETV6::RUNX1 and KMT2A::MLLT3 rearrangements. Chromosomal microarray analysis (CMA) indicated that the breakpoint within KMT2A was located outside the typical region described in KMT2A leukemogenic translocations. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Marie-France Gagnon, James Smadbeck, Neeraj Sharma, Patrick Blackburn, Jonna Demasi Benevides, Yassmine Akkari, Jennifer Jaroscak, Iya Znoyko, Daynna Wolff, Cynthia Schandl, Reid Meyer, Patricia Greipp, Xinjie Xu, Nicole Hoppman, Rhett Ketterling, Jess Pe Source Type: research
79. Implications of fortuitous detection of JAK2 V617F mutations with solid tumor clinical sequencing
Genomic profiling of tumor provides valuable diagnostic, prognostic and therapeutic information. However, as clinical sequencing often relies on tumor-only approaches, factors such as infiltration from cells of hematopoietic lineage may confound accurate inference of variants present in tumor. We sought to investigate the frequency of a hallmark mutation in myeloid malignancies, JAK2 V617F, in solid tumor samples subjected to genetic testing at our institution and whether these underlie coexistence of a hematologic malignancy. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Marie-France Gagnon, Teja Koganti, Beth Pitel, Katherine Geiersbach Source Type: research
80. Evaluation of MYEOV expression in multiple myeloma patients with IGH::CCND1 rearrangement and chromosome 11 polysomy.
The t(11;14)(q13;q32) rearrangement is the most common genetic abnormality in Multiple myeloma (MM). The myeloma overexpressed (MYEOV) gene maps very close to the CCND1 gene on chromosome 11. In vitro studies have shown role of MYEOV in cancer proliferation and invasion. The aim of this study was to investigate the prognostic significance of MYEOV deregulation in a series of primary MM cases. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Shivani Golem, Venkata Rakesh Sethapati, George Kostanian, Kamilla Isakova, Harsh Pathak Source Type: research
81. Discrepancies in the detection of PML::RARA gene rearrangement by FISH using commonly used dual-color dual-fusion probes
Acute promyelocytic leukemia (APL) is a medical emergency with serious complications (e.g., DIC), requires prompt treatment and rapid test turnaround time (TAT) for diagnosis confirmation. APL results from a fusion of the PML gene (15q24) with the RARA gene (17q21) creating a fusion gene on the derivative chromosome 15. There are multiple breakpoints that can occur. PML::RARA is the most common (98%) rearrangement. Fluorescent in situ Hybridization (FISH) study helps in the diagnosis of APL with rapid TAT. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Shivani Golem, Karsten Evans Source Type: research
82. Enabling large scale precision oncology research with a new standard for genomic variants: OMOP Genomic
Precision Oncology requires the application of genomic variants to epidemiological methods used in clinical research. Variants are detected through traditional immunohistochemistry, microarray or PCR panels, or large-scale next generation sequencing, either for purposes of clinical care or understanding of biological processes of carcinogenesis and cancer treatment. However, we see few variants used in standard epidemiological research in the context of rich phenotypes: longitudinal observational patient data of treatment, progression and survival. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Asieh Golozar, Christian Reich Source Type: research
83. Quantum lattices for early cancer detection through machine learning
Cancer is a broad term for diseases characterized by uncontrollable and abnormal cell growth. It is the second-leading cause of death worldwide, with 9 million deaths each year; early cancer detection remains crucial for improving survival outcomes, especially in developing countries. In this research, a novel three-step framework based on quantum machine learning was developed using transcriptome data to identify key cancer biomarkers and combine them to create mathematical expressions that can predict the presence of cancer with high accuracy using the expression levels of five or fewer genes. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Rushank Goyal Source Type: research
84. Benefits of integrating an open-source knowledgebase in a precision oncology workflow
Next-generation sequencing is revolutionizing precision oncology, but vast amounts of sequence data must be processed and mined to reveal clinically relevant alterations that can inform patient care. The Personalized OncoGenomics (POG) program at BC Cancer utilizes whole genome and transcriptome analysis, providing a comprehensive view of advanced cancer patient tumours. This analysis relies on curated clinical knowledgebases linking cancer variants and their clinical relevance, but the breadth and utility of these can be limited by proprietary access or limited coverage. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Cameron Grisdale, Erin Pleasance, Caralyn Reisle, Laura Williamson, Kilannin Krysiak, Jason Saliba, Arpad Danos, Adam Coffman, Susanna Kiwala, Joshua McMichael, Malachi Griffith, Obi L. Griffith, Steven Jones Source Type: research
85. Cell-type-specific genotypic interpretation in the human breast
Understanding the interplay between genetic and epigenetic states is fundamental to the study of development and mechanisms of disease. Most studies that have explored this interplay have leveraged population-scale genotype surveys to associate genetic polymorphisms with epigenetic states in whole blood or other heterogenous tissue types. However, epigenetic states are cell-type specific, raising the possibly of cell-type-specific genetic/epigenetic relationships that could drive specific functional states and disease predisposition. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Axel Hauduc, Annaick Carles, Misha Bilenky, Edmund Su, Martin Hirst Source Type: research
86. Whole genome sequencing of mouse derived cell-free DNA to develop a NF1-MPNST-PDX liquid biopsy model
Malignant peripheral nerve sheath tumors (MPNST) are an aggressive Neurofibromatosis Type 1 (NF1) associated sarcoma with few treatment options. Our lab has generated a series of patient-derived xenograft (PDX) mouse models to assess the efficacy of various treatments in vivo on human tumors. Longitudinal data collection is limited to gross tumor measurements, which fail to provide genomic information in the course of treatment, which may inform mechanisms of treatment resistance. To address this, we have begun to develop a NF1-MPNST-PDX liquid biopsy with the objective of non-invasively collecting sequential genomic data ...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Paul Jones, Wenjia Feng, Xiaochun Zhang, Peter Harris, Taylor Sundby, Faridi Qaium, Jack Shern, Aadel Chaudhuri, Angela Hirbe Source Type: research
87. Somatic mutation variant analysis in rural, resectable non-small cell lung carcinoma patients
In this study, we demonstrate the mutational characteristics and potential for targeted therapy in rural resectable NSCLC patients using whole exome sequencing (WES). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Jussuf Kaifi, Jonathan Mitchem, Amanda Miller, Yariswamy Manjunath, Mouadh Barbirou, Raju Murugesan, Yuanyuan Shen, Guangfu Li, Diego Avella, Aadel Chaudhuri, Chi-Ren Shyu, Wesley Warren, Peter Tonellato Source Type: research
88. Significant association of BRCA1, BRCA2 and TP53 gene polymorphisms with breast cancer risk in Khyber Pakhtunkhwa, Pakistan
Single nucleotide polymorphisms (SNPs) are described as a mutation with a particular prevalence in certain ethinic population that in turn result in the altered prevalence of disease, the tumor suppressor genes responsible for maintaining the genomic stability. Certain SNPs in BRCA1, BRCA2 and TP53 are known to correlate with elevated risk of breast cancer development worldwide, however there is no such study categorizing the risk of breast cancer development in the Khyber Pakhtunkhwa population in Pakistan. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Najeeb Ullah Khan Source Type: research
89. Identification of therapeutic combinations for immune checkpoint inhibitors (ICIs) using explanatory subgroup discovery
Phenotypic and genotypic heterogeneity are characteristic features of cancer. This heterogeneity significantly limits therapeutic response and application, especially in patients without targetable mutations. One example of this is immune checkpoint inhibitors (ICIs), which represent one of the best therapeutic approaches to treat cancer. However, 50% of patients that are eligible for ICI therapy do not respond. Multiple methods for selection have been developed, but still lack the ability to consistently identify patients that will benefit from treatment. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Olha Kholod, William Basket, Danlu Liu, Jonathan Mitchem, Jussuf Kaifi, Chi-Ren Shyu Source Type: research
90. TERT promoter mutation detection by ddPCR in glial atypia
Glial atypia is a frequent 'non-diagnostic' diagnosis in surgical neuropathology and may represent a neoplastic or reactive process. Detection of a TERT promoter (TERTp) mutation in this context would support the diagnosis of neoplasia. Droplet digital PCR (ddPCR) has emerged as a platform with increased sensitivity when compared to next-generation sequencing (NGS). We evaluated the diagnostic yield of TERTp C228T and C250T mutation testing by ddPCR for cases with provided histopathological diagnosis of glial atypia that tested negative by NGS. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Alaa Koleilat, Dragana Milosevic, Cristiane Ida Source Type: research
