46. Data driven refinement of gene signatures for enrichment analysis and cell state characterization
The use of gene expression data has been crucial to the functional characterization of changes in molecular pathway activity and for identifying targets for novel treatments. However, the interpretation of this data is complicated by its high dimensionality and the difficulty of identifying biological signals within a list of differentially expressed genes. Gene Set Enrichment Analysis (GSEA) is a standard method for identifying pathway enrichment in gene expression data by testing whether a set of genes whose expression would indicate the activity of a specific process or phenotype are coordinately up- or downregulated mo...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Alexander Wenzel, Pablo Tamayo, Jill Mesirov Source Type: research
48. Refining the drug-gene interaction database for precision medicine
The Drug-Gene Interaciton Database (DGIdb, www.dgidb.org) is a publicly accessible resource that aggregates over 100,000 drug-gene interaction claims across 30 interaction types aid both researchers and clinicians in identifying associations between genes of interest and available therapeutics. By incorporating peer-reviewed data sources and publications, DGIdb integrates 102,426 gene records and 57,498 drug records from 40 drug-gene interaction data sources to drive hypothesis generation in precision medicine. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Matthew Cannon, James Stevenson, Kori Kuzma, Colin O'Sullivan, Katherine Miller, Olivia Grischow, Adam Coffman, Susanna Kiwala, Joshua McMichael, Dorian Morrissey, Kelsy Cotto, Obi L. Griffith, Malachi Griffith, Alex Wagner Source Type: research
49. Reduced performance of centromere 15 probe in association with African ancestry
Fluorescence in situ hybridization (FISH) is the gold-standard assay to detect genomic abnormalities of prognostic and therapeutic significance in monoclonal gammopathies including multiple myeloma (MM). Hyperdiploid MM, a favorable subtype, is characterized by gains of odd-numbered chromosomes including chromosome 15. Gains of chromosome 15 are found in ∼50% of MM patients with hyperdiploidy, while losses of chromosome 15 are rarely reported. We previously discovered some MM cases had a false-negative chromosome 15 FISH-result using the alpha satellite D15Z4 probe. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Linda Baughn, Alaa Koleilat, Hongwei Tang, James Smadbeck, Neeraj Sharma, Kathryn Pearce, Eran Elhaik, Michael Baird, Xinjie Xu, Jess Peterson, Rhett Ketterling, Vincent Rajkumar, Shaji Kumar, Patricia Greipp, Yan Asmann Source Type: research
50. Molecular profiling of Cytolyt-Fixed FNA washes to improve diagnostic yield in lung cancer
For therapeutic purpose, tumor molecular profiling (MP) of both DNA and RNA is standard-of-care in lung cancer patients. With increased use of fine needle aspiration (FNA) to assist in diagnosis, MP can be challenging given the limited cell block material. At our institution, only 40% of 309 FNA with lung cancer diagnosis over 2 years were successful for DNA and RNA MP as a send out, compared with 90% of surgically-resected specimens. To improve the diagnostic yield, we salvaged left over FNA washes (FW, 30-40mL) from the Cytology Laboratory within a median of 10 days from collection. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Meenakshi Mehrotra, William Lam, Aneta Waluszko, Evelyne Kouame, Maureen Zakowski, Matthew Croken, Jane Houldsworth Source Type: research
51. Discerning cell types and states in spatial transcriptomics data using topic modelling
Glioblastoma multiforme (GBM) is the most common adult brain tumour. GBM cells include a diverse collection of normal and tumour cells with distinct molecular capabilities and with differential levels of sensitivity to treatment that led to treatment resistance. Spatial transcriptomics technologies (e.g. 10X Visium) have enabled analyzing tumour-normal cells interactions in a physical tissue context. Using Visium, a well-annotated cohort of adult GBM patient samples grown as patient-derived xenograft (PDX) models were profiled at different time points of the disease. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Aly Abdelkareem, Sorana Morrissy Source Type: research
52. Novel recurrent cytogenetic abnormalities predict overall survival in tetraploid/near-tetraploid MDS/AML
Tetraploidy (4n=92 chromosomes) and near-tetraploidy (81-103 chromosomes) (T/NT) are uncommon cytogenetic events in MDS/AML ( ∼1%). Most patients are older adults with a male predominance and poor prognosis. Recurrent abnormalities associated with T/NT MDS/AML include -5/del(5q), -7/del(7q), -17/add(17p)/i(17q), -18, +8, and +21. However, other clinically-relevant abnormalities likely remain 'hidden' in long strings of c ytogenetic nomenclature that are difficult to discern by visual inspection. To date, no studies have had the statistical power and computational methodology to identify novel recurrent abnormalities asso...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Lynne Abruzzo, Matthew Avenarius, Zachary Abrams, Ling Guo, James Blachly, Cecelia Miller, Nyla Heerema, Kevin Coombes Source Type: research
53. Clinical whole exome/whole transcriptome (WES/WTS) analysis detects copy number and structural rearrangements important
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: Hussam Al-Kateb Source Type: research
54. CancerTrialMatch: A computational resource for the management of clinical trials at a precision oncology center
The routine use of genetic and genomic sequencing in the treatment of cancer has been steadily rising over the past few years, with a corresponding increase in the availability of biomarker-based clinical trials. At the Avera Cancer Institute, biomarker-based clinical trials are often presented as treatment options to oncologists at the molecular tumor board. This necessitated a way to capture structured trial data, and match them to patients based on their disease and sequencing profile in a systematic manner. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Anu Amallraja, Shivani Kapadia, Padmapriya Swaminathan, Casey Williams, Tobias Meissner Source Type: research
55. Epigenetic therapy-induced transposable element antigens in Glioblastoma
Among the CNS neoplasms, glioblastoma (GBM) is the most common and most lethal. Profiling the GBM histologic, genetic and epigenetic landscapes enables clinical stratification of distinct patient populations with prognostic and therapeutic implications. Despite accounting for nearly half the genome content, transposable elements (TEs) have been underexplored in cancer genomic studies owing to their constitutive epigenetic repression in somatic cells. However, clinical application of DNA methyltransferase (DNMTi) and histone deacetylase inhibitors (HDACi) have demonstrated potent activation of TE-derived alternative transcr...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Noah Basri, Josh Jang, Nakul Shah, Holden Liang, Ting Wang Source Type: research
56. Chr8 gain is associated with MPNST transformation
Malignant Peripheral Nerve Sheath Tumors, or MPNST, are a rare and aggressive tumor accounting for 4% of all sarcomas that often arise from transformation of a benign precursor tumor (Plexiform Neurofibroma or PN). The majority arise sporadically or in the setting of Neurofibromatosis type 1 (NF1), and when advanced or unresectable, can be difficult to treat effectively. Despite advances in our understanding of MPNST pathobiology, there exist few effective therapeutic options, and clinical trials have not identified any successful investigational agents. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Himanshi Bhatia Source Type: research
57. Identification of key molecular mechanisms in IDH-mutant brain tumors to enable precise risk stratification
Isocitrate dehydrogenase 1 and 2 (IDH) mutations are the most prevalent genetic alterations in adult low-to intermediate grade diffuse astrocytomas, anaplastic astrocytomas, and oligodendrogliomas. Previous studies of adult IDH-mutant tumors have revealed unique tumor-specific signatures, allowing for stratification based on molecular phenotype and clinical presentation. However, very little is known about pediatric IDH-mutant tumors, resulting in fragmented clinical care.To perform precise molecular profiling of IDH-mutant brain tumors to predict patient outcomes and guide potential future therapeutic developments. (Sourc...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Surajit Bhattacharya, Adam Dawood, Hayk Barseghyan, Eric Vilain, Miriam Bornhorst Source Type: research
58. Improving the molecular diagnosis of SBDS-related disorders by identifying rare gene conversion events.
Biallelic disease-causing variants in the SBDS gene account for over 90 percent of Shwachman-Diamond Syndrome, a congenital autosomal recessive disorder characterized by pancreatic insufficiency, hematological malfunction, and skeletal abnormalities. Molecular genetic tests of SBDS include single-gene Sanger sequencing or next generation sequencing (NGS) panels. The detection of SBDS variants by either method, however, is complicated by the pseudogene, SBDSP1. In fact, common disease variants in SBDS are created by gene conversion events between SBDS and SBDSP1, making it difficult to determine whether a variant affects th...
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Casey Brewer, Kristen Sund, Xinjian Wang, Jie Liu, Qiaoning Guan, Wenying Zhang, Brian Dawson, Yaning Wu Source Type: research
59. Inferring copy number events in Glioblastoma using spatial gene expression data
Glioblastoma (GBM) is the most common malignant brain tumour in adults, with inevitable treatment resistance and poor outcomes. Genomic instability of GBM gives rise to large-scale chromosomal copy number variants (CNVs) that drive resistance. Genetically distinct clones in GBM are conventionally investigated using whole-genome sequencing (WGS), but recent bioinformatic approaches can infer CNVs using transcriptomics data only. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Samuel Brown, Aly Abdelkareem, Aaron Gillmor, Heewon Seo, Kata Osz, Jennifer A. Chan, Sorana Morrissy Source Type: research
60. Panning for neoantigens to demonstrate feasibility of neoantigen vaccines in canine melanoma
Canine malignant melanoma (CMM) mimics human melanoma in invasiveness, metastatic behavior, and limited survival. Novel immunotherapies could target CMM neoantigen expression to dissect mechanisms of success and failure in a naturally occurring model of cancer. Tools to predict and validate canine MHC I presentation of neoantigens must be optimized to select candidate vaccine peptides.Tissues and a cell line from a dog responding in a trial of an autologous deglycosylated melanoma vaccine were selected. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Jeffrey Bryan, Zachary Skidmore, Hansjorg Rindt, Shirley Chu, Brian Fisk, Catrina Fronick, Robert Fulton, Mingyi Zhou, Nathan Bivens, Brian Mooney, Pei Liu, Carol Reinero, Malachi Griffith, Obi L. Griffith Source Type: research
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
