61. Clinical whole exome/whole transcriptome analysis detects clinically relevant structural alterations in Multiple Myeloma
Chromosomal copy number alterations (CNAs) and structural rearrangements (SR) are a key part of risk stratification and management of patients with MM. We developed a clinical paired tumor/normal WES/WTS assay that detects CNAs at one-copy difference from focal to whole genome, and gene fusion at 20% and 10% limit of detection, respectively. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Maria Nieves Calvo, Sean Caruthers, Joseph Tripodi, Jane Houldsworth, Marc Fink, Scott Newman, Rong Chen, Wanying Zhang, Liu Liu, Yong Shi, Tomi Jun, Ken Onel, William Oh, Lisa Edelmann, Eric Schadt, Michael Rossi, Feras Hantash, Hussam Al-Kateb Source Type: research
62. Molecular profile of patients with Acute Myeloid Leukemia at diagnosis
The characterization of the molecular profile in acute myeloid leukemia (AML) is essential for diagnosis, prognosis, risk stratification and therapeutic management. The aims of this study were: 1) To evaluate the molecular profile of patients with acute myeloid leukemia in a clinical laboratory at diagnosis and 2) To evaluate the sensitivity of different strategies for detection of FLT3 ITD mutation. We included 118 patients with a diagnosis of acute AML from March 2018 to December 2021 from a single diagnostic center. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Paulo Campregher, Susana Rosa, Caroline Silveira, Larissa Lima, Jo ão Bosco de Oliveira, Karla Pelegrino Source Type: research
63. Comparative analysis of testing methods used for the detection of internal tandem duplications in the KMT2A/MLL gene
The Lysine (K)-Specific Methyltransferase 2A (KMT2A) gene (formerly MLL) that resides on human chromosome 11q23 is frequently rearranged in de novo and therapy related leukemia. KMT2A translocations with various partner genes are often easily detected by classic molecular and cytogenetic approaches. However, the detection of small intragenic insertions, the partial tandem duplications of the KMT2A gene (KMT2A-PTD), is challenging. Additional co-occurring alterations, such as Trisomy 11 which alerts one to the PTD, may further hamper the identification of KMT2A-PTD. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Jos é-Mario Capo-Chichi, Andrew Seto, Olivia King, Shabnam Salehi-Rad, Ana Baptista, Grenier Sylvie, Bev Nwachukwu, Anne Tierens, Andrea Arruda, Mark Minden, Adam Smith Source Type: research
64. FAIR sharing of cancer GWAS data via the NHGRI-EBI GWAS catalog
The GWAS Catalog is a comprehensive resource of data from genome wide association studies. Top associations and detailed metadata are made available in a standard format alongside full p-value summary statistics. These are re-used by the genomics community, e.g. in meta-analyses, generation of polygenic scores, identification of new drug targets. As of February 2022, the Catalog contains 33,162 GWA studies including 22,675 with summary statistics, from 5,595 publications - covering>5,000 distinct traits. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Maria Cerezo, Annalisa Buniello, Ala Abid, Peggy Hall, James Hayhurst, Arwa Ibrahim, Sajo John, Elizabeth Lewis, Aoife McMahon, Abayomi Mosaku, Santhi Ramachandran, Elliot Sollis, Fiona Cunningham, Paul Flicek, Lucia Hindorff, Laura Harris, Helen Parkinso Source Type: research
65. AR/enhancer alterations in metastatic castrate-resistant prostate cancer patient plasma predicts worse overall survival
Androgen-receptor signaling inhibitors (ARSI) such abiraterone and enzalutamide have significantly improved clinical outcomes in patients with metastatic castrate-resistant prostate cancer (mCRPC). However, patients with genomic alterations in androgen receptor (AR) and its enhancer region do not respond well and acquire resistance to these inhibitors. We previously developed a cell-free DNA (cfDNA) liquid biopsy assay (EnhanceAR-Seq) that can detect alterations in AR locus including the upstream enhancer. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Pradeep Chauhan, Alexander Shiang, Ha Dang, Jace Webster, Elisa Ledet, Ramandeep Babbra, Wenjia Feng, Peter Harris, Faridi Qaium, Ellen Jaeger, Patrick Miller, Sydney Caputo, Giordano Santos, Russell Pachynski, A. Oliver Sartor, Christopher Maher, Aadel C Source Type: research
66. Optical genome mapping workflow for Somatic Abnormality detection in Multiple Solid Tumor types
Solid tumors are often characterized by a high degree of complex somatic structural variants of multiple classes, especially rearrangements and copy number variants. Characterizing this genomic complexity is crucial for understanding the biology behind carcinogenesis but is challenging as a result of limitations of current genomic technology classes: cytogenic (low resolution) and molecular (poor sensitivity for structural variation). Accurate assessment of genomic structural variation is important because some tumors acquire growths advantage by amplifying or creating oncogenes by fusing otherwise non-pathogenic genes and...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Benjamin Clifford, Andy Wing Chun Pang, Mark Oldakowski, Alka Chaubey, Alex Hastie Source Type: research
67. Long noncoding RNAs encoding peptides in cancer
Long noncoding RNAs (lncRNAs) have biological and clinical significance in cancer, but their mechanisms remain underexplored. One emerging mechanism includes translation of small peptides with reported roles in cancer progression from annotated lncRNAs, highlighting the need for efficient mechanism prediction and validation of specific candidates. Through comprehensive proteogenomic analysis, we found several additional well-known oncogenic lncRNAs and uncharacterized, cancer type-specific lncRNAs with support for peptide coding capabilities. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Emily Coonrod, Ghofran Othoum, Andrew Nickless, Jin Zhang, Matthew Inkman, Sidi Zhao, Ha Dang, Jace Webster, Emily Rozycki, Sherron Fontes, Nicole White, Christopher Maher Source Type: research
68. Integrative analysis of genomic and transcriptomic data using RegTools to identify splice-altering mutations within bulk
The interpretation of variants in cancer is often focused on genomic alterations that have a known coding consequence. This analysis strategy excludes somatic mutations in non-coding regions of the genome and even exonic mutations that may have unidentified regulatory consequences. To address this issue, we created RegTools, a software suite that integrates analysis of variant calls from genomic data with evidence of expressed splice junctions from transcriptomic data to efficiently identify variants that may cause aberrant splicing in tumors. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Kelsy Cotto, Yang-Yang Feng, Avinash Ramu, Megan Richters, Sharon Freshour, Zachary Skidmore, Joshua McMichael, Jason Kunisaki, Yiing Lin, William Chapman, Christopher Maher, Vivek Arora, Gavin Dunn, Ravindra Uppaluri, Ramaswamy Govindan, Obi L. Griffith, Source Type: research
69. Integration of standards for variant oncogenicity into the CIViC data model
Somatic cancer variant oncogenicity holds great importance. Evidence demonstrating oncogenic or benign variant effects may have clinical implications. For example, in colorectal cancer, an activating KRAS mutation will preclude EGFR inhibitor treatment, but guidelines may allow EGFR administration if KRAS mutation is benign.Therefore it is clear that a rigorous method for assessing variant oncogenicity is crucial.A method exists for assessing pathogenicity of germline variants developed between ACMG and AMP, and guidelines from AMP/ASCO/CAP classifying somatic variants are widely used for therapeutic, prognostic and diagno...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Arpad Danos, Kilannin Krysiak, Jason Saliba, Susanna Kiwala, Joshua McMichael, Adam Coffman, Erika Barnell, Kana Sheta, Nicholas Spies, Cameron Grisdale, Alex Wagner, Malachi Griffith, Obi L. Griffith Source Type: research
70. Assessment of circulating tumor DNA tumor mutational burden to define resistance in HR+ HER2- metastatic breast cancer
Identifying subsets of patients with baseline resistance to endocrine therapy (ET) combined with CDK4/6 inhibition (CDK4/6i) is challenging. Our study examined circulating tumor DNA (ctDNA) using whole-exome sequencing to derive blood tumor mutational burden (bTMB) and mutational signatures to assess patients with early progression on ET + CDK4/6i. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Andrew A. Davis, Jingqin Luo, Tiantian Zheng, Xiaoxi Dong, Lu Tan, Amy Wang, Rama Suresh, Foluso Ademuyiwa, Caron Rigden, Timothy Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Pavan K. Tandra, Tracy Summa, Britney Haas, Shana Thomas, Le Source Type: research
71. Genetic predisposition to hematopoietic neoplasms: Single-site experience
Hematopoietic neoplasm testing generally involves sequencing of recurrent genes found to be mutated in these cancers. A few genes are detected in both germline and somatic-derived malignancies; however, ANKRD26 and DDX41 are previously only associated with germline predisposition and not detected in somatic-derived cancers, and often not included on sequencing panels. Our institution utilizes a panel including both genes and the findings have underscored the value of testing for these alterations. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Celeste Eno, Wenjuan Zhang, Eric Vail Source Type: research
72. Variant curation of BCR::ABL1-like B-lymphoblastic leukemia/lymphoma through expert panel consensus
BCR::ABL1-like B-lymphoblastic leukemia/lymphoma (B-ALL) is a neoplasm of precursor B cells and a subtype of high-risk B-ALL that exhibits a gene expression profile similar to that of BCR::ABL1-positive B-ALL while lacking the BCR::ABL1 fusion protein. Instead, it is characterized by somatic variants in a variety of cytokine receptor and kinase encoding genes. This genetic heterogeneity poses challenges for accurate and comprehensive laboratory diagnosis and clinical decision making including prognostication and therapeutic interventions. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Mark G. Evans, Jason Saliba, Yassmine Akkari, Deepa Bhojwani, Piers Blombury, Arpad Danos, Paul G. Eckert, Mark D. Ewalt, Sandeep Gurbuxani, Christine J. Harrison, Ilaria Iacobucci, Shai Izraeli, Nitin Jain, Rashmi Kanagal-Shamanna, Chim ène Kesserwan, A Source Type: research
73. Chromosomal microarray-based genomic profiling of T-cell Large Granular Lymphocyte Leukemia
T-cell large granular lymphocyte (T-LGL) leukemia is a rare lymphoproliferative disorder characterized by infiltration of blood and bone marrow with large granular lymphocytes, splenomegaly, and cytopenias. Most patients with T-LGL leukemia follow an indolent course, with a median survival of over 10 years. However, a subset of T-LGL leukemia cases exhibits more aggressive clinical behavior. Recent identification of recurrent activating STAT3 gene mutations in T-LGL leukemia suggests that sequence alterations play a role in the persistence of clonal T-cell expansions. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Jinbo Fan, Lei Wang, Eli Williams Source Type: research
74. Genetic and functional characterization of complex chromosomal rearrangements in a family with multisystem anomalies
Complex chromosomal rearrangements (CCRs) are rare structural variants which involve three or more chromosomal breakpoints and are usually de novo in most reported cases. Traditional molecular cytogenetics approaches using karyotyping, fluorescence in situ hybridization (FISH) and chromosome microarray analysis (CMA) have been used clinically to diagnose CCRs. However, each of these standard tests has limitations, including low resolution causing difficulty in detecting cryptic rearrangements, imprecise breakpoint mapping, or inability to detect balanced rearrangements. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: He Fang, Whitney Neufeld-Kaiser, Yajuan Liu Source Type: research
75. Clinical implementation of a precision medicine consultation service
To realize precision medicine, clinicians need to apply a growing number of diagnostic tests. Each test result relies on specific domain expertise; however, integration across a variety of diagnostics poses unique challenges-including financial sustainability of the consultation service. Recent 2022 billing code updates emphasize the value of consultations. Here, we present the design and implementation of a clinical pathology consultation workflow. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Abigail Finer, Andrea Pannone, Adam Bard, Ursula Green, Esther Baranov, Lauren Ritterhouse, Dora Dias-Santagata, Jochen Lennerz Source Type: research
