EML4-ALK Variant 3a/b as a mechanism of osimertinib resistance in a patient with EGFR L858R positive NSCLC
In September 2019, a 74-year-old woman was introduced to our hospital because of persistent right chest pain. She had a history of smoking (50 pack-years) and had undergone surgery for right breast cancer at 40 years of age without recurrence. Chest computed tomography (CT) revealed a mass in the upper lobe of the right lung (Figure 1A). She underwent CT-guided lung biopsy and was diagnosed with lung adenocarcinoma stage IVB (cT4N2M1c) with multiple lung and bone metastases. Bone metastases were detected in the transverse processes of the thoracic spine on PET at diagnosis; however, the effect of treatment was difficult to...
Source: Cancer Genetics and Cytogenetics - December 8, 2023 Category: Genetics & Stem Cells Authors: Teppei Yamaguchi, Katsuhiro Masago, Eiichi Sasaki, Hiroaki Kuroda, Hirokazu Matsushita, Yoshitsugu Horio Tags: Case Report Source Type: research
Clinical whole-genome sequencing and FISH identify two different fusion partners for NUP98 in a patient with acute myeloid leukemia: a case report
Only rare cases of acute myeloid leukemia (AML) have been shown to harbor a t(8;11)(p11.2;p15.4). This translocation is believed to involve the fusion of NSD3 or FGFR1 with NUP98; however, apart from targeted mRNA quantitative PCR analysis, no molecular approaches have been utilized to define the chimeric fusions present in these rare cases. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 29, 2023 Category: Genetics & Stem Cells Authors: Bahareh A. Mojarad, Zachary D. Crees, Molly C. Schroeder, Zhifu Xiang, Justin Vader, Jason Sina, Meagan Jacoby, John L. Frater, Eric J. Duncavage, David H. Spencer, Kory Lavine, Julie A. Neidich, Ina Amarillo Tags: Case Report Source Type: research
1. Clinical validation of plasma whole genome sequencing for detection of minimal residual disease from solid tumours
Plasma whole genome sequencing of peripheral blood cell-free DNA (cfDNA) can sample the mutational spectrum of a tumour to enable minimal residual disease (MRD) detection without serial, invasive tissue collections. We validated the use of plasma WGS for detection of MRD in a CAP/CLIA/ACD-accredited laboratory using the MRDetect algorithm. We prepared libraries using automated and manual workflows across cfDNA inputs from 1-50 ng. We determined that cfDNA input levels down to 10 ng, using both automated (88 samples/run) and manual (14 samples/run) workflows, yielded comparable and reproducible duplication rates0.2 reads / ...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Felix Beaudry, Lubaina Kothari, Savo Lazic, Kristie Ng, Sharanjit Singh, Theodore Chan, Faridah Mbabaali, Andrea Bevan, Samy Danial, Sarah Donald, Austin Devries, Alexander Fortuna, Iain Bancarz, Ilinca lungu, Madhuran Thiagarajah, Jessica Miller, Carolyn Source Type: research
2. Personalized sequencing assays for cerebrospinal fluid liquid biopsies in children with brain tumors
Conventional methods for monitoring children with high-grade central nervous system (CNS) tumors include magnetic resonance imaging and cytological assessment of cerebrospinal fluid (CSF), but these methods often miss detection of minimal residual disease (MRD). Molecular techniques have evolved, allowing use of next-generation sequencing (NGS) to detect tumor-derived cell-free DNA (cfDNA) in peripheral biofluids (e.g., blood, urine, CSF) - coined `liquid biopsies.' Here, we describe the development of personalized sequencing assays for CSF liquid biopsies using the patient's tumor DNA profile known from prior exome sequen...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Katherine Miller, Sarah Wilson, Adithe Rivaldi, Olivia Grischow, Jocelyn Lucyshyn, Lakshmi Venkata, Kyle Voytovich, Heather Costello, Peter Chang, Ben Kelly, James Fitch, Margot Lazow, Anthony Miller, Elaine Mardis Source Type: research
3. Application of optical genome mapping to identify samples with homologous recombination deficiency
Certain cancer treatments have been shown to be effective in killing cancer cells exhibiting genome instability signatures indicative of homologous recombination deficiency (HRD). There are three measurements of HRD signatures commonly employed: loss of heterozygosity (HRD-LOH), telomeric allelic imbalance (TAI) and large-scale state transition (LST). Current genomic technologies lack sensitivity to capture the full extent of somatic variants related to HRD and this limits their sensitivity.Here, optical genome mapping (OGM) was used to detect large structural variants (SVs) and calculate a HRD score. (Source: Cancer Genet...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Alex Hastie, Andy Wing Chun Pang, Nikhil Sahajpal, Daniel Saul, Ravindra Kolhe, Alka Chaubey Source Type: research
4. Comprehensive next generation cytogenomics improves risk stratification of acute myeloid leukemia
Cytogenetic diagnostics including karyotyping, FISH, and chromosome microarray are regularly applied in cases of suspected leukemia, including acute myeloid leukemia (AML). Each of these three tests can identify non-overlapping sets of chromosome aberrations known to have prognostic or diagnostic value. Because each test addresses different classes of prognostic variants, all three tests are often performed in series or in parallel, adding time and expense to the diagnostic process. Here we describe OncoTerra, a platform based on proximity ligation sequencing (PLS), that can be used to identify variants commonly assayed by...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Stephen Eacker, Alexander Muratov, Maika Malig, Brad Nelson, Mary Wood, Michael VanDyke, Kyle Langford, Lan Beppu, Olga Sala-Torra, Cecilia Yeung, Shawn Sullivan, Ivan Liachko, Jerald Radich Source Type: research
5. Overcoming challenges in semantic alignment of therapeutics knowledge using TheraPy
Genomic medicine pipelines incorporate knowledge extracted from an increasing number of publicly available databases. Unfortunately, integration of data about drugs and other therapeutics remains challenging, as these concepts are often ambiguous and inconsistently described. Semantic alignment of this knowledge would enable richer genomic annotation and clinical decision support, but is hampered by incongruities regarding data structure and scope between knowledge sources. Individual therapeutics may be associated with a variety of related concepts, from developmental identifiers and IUPAC chemical structure names to acti...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: James Stevenson, Matthew Cannon, Alex Wagner Source Type: research
6. Tracking immunotherapy response with single cell T cell receptor profiling in canine models of cancer
Spontaneous cancers in companion dogs are increasingly recognized as robust models of human disease. The ability to track tumor-specific immune responses in these models would benefit from reagents to perform species-specific single cell T cell receptor sequencing (scTCRseq). To date, scTCRseq and its integration with scRNA data have not been demonstrated for canine samples. Five healthy dogs, two dogs with T cell lymphoma and four dogs with melanoma in a trial of an autologous deglycosylated melanoma vaccine were selected to demonstrate applicability of scTCRseq in a cancer immunotherapy setting. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Obi Griffith, Zachary Skidmore, Hans Rindt, Shirley Chu, Bryan Fisk, My Hoang, Catrina Fronick, Robert Fulton, Mingyi Zhou, Nathan Bivens, Carol Reinero, Malachi Griffith, Jeff Bryan Source Type: research
7. AI-Based Algorithms for neoplastic metaphase cells boost efficiencies in the cytogenetics laboratory
Traditionally, clinical cytogenetics laboratories analyzing digitized images of metaphase spreads have relied upon manual keystrokes and mouse clicks within the software to separate and classify individual chromosomes for review. These are time-consuming, error-prone tasks that add labor costs and risks to quality. We implemented artificial intelligence (AI)-assisted digital image analysis of metaphase chromosomes in our laboratory for hematologic oncology cases to improve overall turnaround time and quality. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Bo Hong, Brian Fedderson, Jian Zhao, Erica Andersen Source Type: research
8. Mapping variants from multiplex assays of variant effect (MAVEs) to human reference sequences
The accurate clinical assessment of variant pathogenicity and oncogenicity requires structured, computable evidence. A critical type of evidence used in this assessment is the functional impact of genetic variants derived from functional assays, but effects for individual variants may not be easily retrievable, hindering variant assessment. The Atlas of Variant Effects Alliance is working to address this problem by standardizing the structure and dissemination of multiplex assays of variant effect (MAVE) data, but the assay-specific sequences used to generate these data make translations to human genomics databases challen...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Jeremy Arbesfeld, Kori Kuzma, Kevin Riehle, Julia Foreman, Sumaiya Iqbal, Melissa Cline, Alan Rubin, Alex Wagner Source Type: research
9. Implementation survey of the ACMG/CGC standards for interpretation of acquired CNAs and CN-LOH in neoplastic disorders
These standards introduced a categorization system for the interpretation and reporting of acquired CNAs and CN-LOH in neoplastic disorders (PMID: 31138931). Three years after their publication, the workgroup developed a survey to gauge implementation of the standards in clinical laboratories. Part 1 of the survey was focused on clinical implementation data and part 2 on laboratory practices. The survey was distributed through CGC, and 32 responses from 4 continents were received. 75% of participants reported that they either fully or partially implemented the standards in their laboratories. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Fady Mikhail, Jaclyn A. Biegel, Adrian M. Dubuc, Betsy Hirsch, Scott Newman, Lina Shao, Daynna J. Wolff, Gordana Raca Source Type: research
10. Current state of diagnostic testing in pediatric sarcoma: practical solutions to diagnostic challenges
The Sarcoma Working Group of the Cancer Genomics Consortium (CGC) aims to understand the current state of diagnostic testing for pediatric sarcomas and the challenges faced in the field. We conducted a survey of CGC general constituents and American Cytogenetics Forum members (CYTOGN-L@LISTSERV.SC.EDU) in April/May 2022. In total, 46 responses were received, predominantly from university/academic/teaching hospitals (n=45) in the United States (n=41) and Canada (n=5). Respondents reported diverse roles including laboratory directors (n=25), pathologists (n=15), oncologists (n=3), and laboratory technologists (n=3). (Source:...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Kathleen Schieffer, Renu Bajaj, Selene Koo, Josee Lavoie, Dolores Lopez-Terrada, Xinyan Lu, Minjie Luo, Thuy Phung, Maxine Sutcliffe, Daynna Wolff, Jennelle Hodge Source Type: research
11. Evaluation of Hi-C versus optical genome mapping for diagnosing constitutional genomic structural variants
Accurate diagnosis, prognosis, and management of genetic diseases require precise characterization of genomic structural variants (GSVs). However, current methods, such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA), have limitations that preventing a comprehensive understanding of GSVs and are often ordered reflexively in the clinical setting. To overcome these limitations, we implemented proximity ligation sequencing (Hi-C), which can capture ultra-long-range genome contiguity information, and compares it to optical genome mapping (OGM). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: He Fang, Yajuan Liu, Steve Eacker, Whitney Neufeld-Kaiser Source Type: research
12. Endothelial cells are a key target of IFN-g during response to combined PD-1/CTLA-4 ICB treatment in bladder cancer
Bladder cancer is the tenth most common cancer worldwide, accounting for over 500,000 new cancer cases and 200,000 cancer-related deaths per year. In recent years, use of immune checkpoint blockade (ICB) treatments for bladder cancer has become more common and several PD-1/PD-L1 inhibitors have been approved by the FDA for treatment of bladder cancer. However, clinical trials of PD-1/PD-L1 monotherapy show response rates of only ∼30%, indicating many patients are not receiving benefit from ICB treatments. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Sharon Freshour, Bryan Fisk, Timothy Chen, Haolin Shen, Matthew Mosior, Zachary Skidmore, Catrina Fronick, Jennifer Bolzenius, Obi Griffith, Vivek Arora, Malachi Griffith Source Type: research
13. HPV forms chimeric virus-human transcripts that affect host gene expression in cervical tumors
Cervical cancer is a common gynecological tumor, primarily caused by HPV infection. Integration of HPV into the human genome allows aberrant expression of HPV oncogenes E6 and E7. However, whether HPV-human gene fusions arise from these events and their effects on human gene partners are less studied. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Kay Jayachandran, Rashmi Pillai, Matthew Inkman, Fiona Ruiz, Jace Webster, Julie Schwarz, Christopher Maher, Jin Zhang Source Type: research
