14. Concurrent systemic mastocytosis and T-lymphoblastic lymphoma unified by a novel cryptic JAKMIP2::PDGFRB rearrangement
Rearrangements leading to constitutive PDGFRB activity are a rare cause of myeloid/lymphoid neoplasms, usually presenting as myelodysplastic/myeloproliferative neoplasms with prominent eosinophilia. These rearrangements are generally detectable by conventional karyotyping and are important to identify as they typically confer sensitivity to imatinib. Here we report a unique case of a myeloid/lymphoid neoplasm with cryptic PDGFRB rearrangement that presented as an unusual combination of T-lymphoblastic lymphoma (T-LBL) and systemic mastocytosis (SM). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Kevin Shopsowitz, Zeid Hamadeh, Ryan Stubbins, Hayley Merkeley, Helene Bruyere, Mohammad Bahmanyar, Eric McGinnis Source Type: research
15. Loss of MSH2 and MSH6 is frequently observed in prostate neoplasms with mismatch repair deficiency
Deficiency in DNA mismatch repair function in neoplasms can be assessed through immunohistochemical (IHC) analysis of MLH1, MSH2, MSH6, and PMS2 proteins to detect loss of expression of the mismatch repair (dMMR) proteins. dMMR is an FDA-approved, histology-agnostic biomarker for the use of pembrolizumab during specific anti-programmed cell death 1 (PD-1)-based immune checkpoint inhibitor (ICI) therapy regimens. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Gokce Toruner, Richard Yang Source Type: research
16. ClinGen Cancer Variant Interpretation (CVI) Committee: Pilot guidance for somatic cancer variant curation expert panels
The Clinical Genome Resource (ClinGen) Somatic Cancer Variant Interpretation Committee (CVI) provides oversight of the 4-step Somatic Cancer Variant Curation Expert Panel (SC-VCEP) process. The 30 members of the CVI represent broad and diverse expertise from academic, clinical and commercial laboratories. Currently, five SC-VCEPs are underway.The FDA-recognized ClinGen germline expert panel process includes testing of ∼40 pathogenic, uncertain and benign variants to pilot ACMG/AMP specifications. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Deborah Ritter, Eric Duncavage, Julia Elvin, Garrett Frampton, Dean Pavlick, Obi Griffith, Malachi Griffith, Katherine Janeway, Tracy Lively, Laura Macconaill, Matthew McCoy, Funda Meric-Bernstam, Jason Merker, Charles G. Mullighan, Donald (Will) Parson Source Type: research
17. Djerba: A modular system to generate clinical genome interpretation reports for cancer
We present Djerba, a software package for the translation of bioinformatic pipeline output from individual tumor genomes and transcriptomes into clinical reports for precision cancer medicine in a CAP/CLIA/ACD accredited laboratory. Specific use cases are clinical genome and transcriptome sequencing for therapeutic assignment; along with cell-free DNA sequencing using targeted panels and whole genome sequencing, for early cancer and minimal residual disease detection.The modular structure of Djerba enables it to process a wide variety of data, with reports customized for available inputs; rapid development of new reporting...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Iain Bancarz, Felix Beaudry, Aqsa Alam, Alexander Fortuna, Trevor Pugh Source Type: research
18. Investigation of pathogenic and truncated variants of RUNX1 and DDX41 in All of Us
Myeloid neoplasms associated with germline disposition can be caused by inherited variants involving multiple genes such as RUNX1, DDX41, CEBPA, GATA2, ETV6, TP53, ANKRD26s. Inherited pathogenic/likely pathogenic (P/LP) variants of RUNX1 lead to familial platelet disorder with predisposition to myeloid malignancy (FPDMM), and those of DDX41 lead to late onset MDS/AML. However, previous generated data has mostly focused on clinically ascertained probands and their families and thus may be subjected to ascertainment biases. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Huan Mo, Tam C. Tran, Tracey Ferrara, Caralynn Wilczewski, Turner Clesson, Rashmi Kanagal Shamanna, Joshua Denny Source Type: research
19. Developing a generalized model for variants in CIViC
Increased clinical use of next generation sequencing has generated a variant interpretation bottleneck. CIViC (Clinical Interpretations of Variants in Cancer; civicdb.org) addresses this problem by leveraging crowdsourced literature and abstract curation with expert moderation in a completely free and open worldwide resource. The CIViC data model incorporates established and emerging guidelines for classification, and associates evidence to single or multi-variant Molecular Profiles (MPs).Large-scale alterations involving multiple genes and non-genic regions are clinically important in multiple cancers. (Source: Cancer Gen...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Arpad Danos, Kilannin Krysiak, Jason Saliba, Susanna Kiwala, Joshua McMichael, Adam Coffman, Cameron Grisdale, Mariam Khanfar, Obi Griffith, Malachi Griffith Source Type: research
20. Comparative analysis of RNA expression identifies druggable targets in difficult-to-treat pediatric solid tumors
Most pediatric cancers have a low incidence of actionable somatic mutations. Here we examine the clinical utility of incorporating comparative analysis of RNA expression (CARE) into the molecular workup of recurrent/refractory and rare pediatric tumors. Patients treated at Stanford Medicine Children's Health (n=33) with a recurrent/refractory or rare pediatric solid tumor underwent tumor RNA sequencing (RNA-seq) analysis and standard-of-care tumor DNA profiling. The Treehouse Childhood Cancer Initiative compared each patient's tumor RNA-seq profile with over 11,000 uniformly analyzed tumor profiles from public data reposit...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Yvonne Vasquez, Lauren Sanders, Holly Beale, Geoffrey Lyle, Ellen Kephart, Katrina Learned, Drew Thomson, Jennifer Peralez, Amy Li, Min Huang, Kimberly Pyke-Grimm, Sofie Salama, David Haussler, Isabel Bjork, Serena Tan, Sheri Spunt, Olena Vaske Source Type: research
21. Comprehensive `Omic' profiling reveals `Atypical Oligodendrogliomas' which challenge CNS diagnostic classification
Comprehensive `omics' profiling has led to improved classification of adult diffuse gliomas. In addition to histopathology review, diagnostic evaluation of these entities currently necessitates routine molecular analysis of both IDH1/2 mutations and 1p/19q whole-arm co-deletion status in order to accurately distinguish oligodendroglioma (IDH-mutant, 1p/19q whole-arm co-deleted) from IDH-mutant astrocytoma (IDH-mutant,1p/19q-retained) and IDH-wildtype glioblastoma. From a retrospective review of nearly 2000 adult gliomas profiled via chromosomal microarray and targeted next-generation sequencing (NGS), we identified a rare ...
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Adrian Dubuc, David Meredith, Keith Ligon Source Type: research
22. Cell-free DNA genomic and epigenomic analysis to predict survival in mCRPC patients treated with AR-directed therapy
We previously developed a hybrid-capture cell-free (cf) DNA approach to measure genomic alterations within the androgen receptor (AR) gene and its enhancer called EnhanceAR-Seq, and demonstrated that assay-positive patients during/after treatment with AR-directed therapy have significantly worse survival outcomes. Here, we extend these findings to the pre-treatment setting and further develop a companion methylation cfDNA assay to understand molecular changes and predict resistance to AR-directed therapy. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Pradeep Chauhan, Irfan Alahi, Alexander Shiang, Jace Webster, Ha Dang, Lilli Greiner, Breanna Yang, Elisa Ledet, Ramandeep Babbra, Wenjia Feng, Peter Harris, Ellen Jaeger, Patrick Miller, Sydney Caputo, Giordano Santos, Oliver Sartor, Russell Pachynski, C Source Type: research
23. Optical genome mapping reveals new insights into ZFTA fusion in supratentorial ependymomas
Supratentorial ependymoma, ZFTA fusion positive, is a subtype of ependyoma with a ZFTA (C11orf95) fusion, most often involving RELA as the partner. ZFTA rearrangements were initially reported to result from intrachromosomal deletions or chromothripsis in chromosome 11 which are typically detected by chromosomal microarray analysis (CMA). We use CMA, our OncoKids NGS panel, and whole transcriptome RNA-seq to identify ZFTA fusions in pediatric brain tumors. For several tumors with ZFTA fusions detected by RNA-seq, complex copy number alterations involving chromosome 11 were not detected by CMA. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Jianling Ji, Jennifer Cotter, Ben Clifford, Jennifer Han, Cindy Fong, Dharmadhikari V. Avinash, Debra Hawes, Gordana Raca, Jaclyn Biegel Source Type: research
24. Clinical utility of optical genome mapping: comparison with standard cytogenomics work-up for hematological malignancies
In this study, we assessed the clinical utility of OGM compared to SCW in our laboratory. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Gokce Toruner, Zhenya Tang, Rashmi Kanagal-Shamanna, L. Jeffrey Medeiros, Guilin Tang Source Type: research
25. High-risk genetic variants underlie unfavorable prognosis of B-lymphoblastic leukemia patients of Hispanic ethnicity
Compared to other ethnicities, Hispanics have a high incidence of acute lymphoblastic leukemia (ALL), enrichment of unfavorable ALL genetics and worse outcomes, even after correcting for socioeconomic factors. We previously demonstrated increased incidence of the high-risk genetic drivers IKZF1 deletion and IGH::CRLF2 rearrangement in Hispanics compared to non-Hispanic children with B-ALL (Raca et al. Leukemia 2021). Here in an expanded cohort, we sought to 1) validate this finding and 2) identify novel genetic drivers and secondary genetic alterations in B-ALL associated with Hispanic ethnicity. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Maximilian Wengyn, Alexandra E. Kovach, Andrew Doan, My H. Vu, Gordana Raca, Deepa Bhojwani Source Type: research
26. Improving interoperability of therapeutics and their targets for clinical and precision medicine applications
Contemporary genomic medicine pipelines are enabled by integration of genomic and therapeutic knowledge bases for clinical decision support systems. Human curators are expected to synthesize these data to predict how patient tumors will respond to potential therapeutics. In some tumors, the presence of a single mutation can be enough to promote sensitivity to a particular treatment. While gene specific drug interaction information is readily available through many resources, therapeutic ontologies and vocabularies supporting these data are not well aligned. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Matthew Cannon, James Stevenson, Kathryn Stahl, Adam Coffman, Susanna Kiwala, Joshua McMichael, Kelsy Cotto, Obi Griffith, Malachi Griffith, Alex Wagner Source Type: research
27. Five-year experience of evaluating individuals at-risk for underlying genetic predisposition to hematologic malignancy
In 2018, the Fred Hutchinson Cancer Center Hematologic Malignancy Genetics and Surveillance clinic was established. This is a multidisciplinary clinic which offers personalized diagnosis, risk assessment, and surveillance care to adult patients and family members with known or suspected genetic predisposition for hematologic cancers. From January 2018 to February 2023, 190 patients (ages 16-73 yo, average age 45 yo) from 74 families completed consultations. Utilizing the Fred Hutch's Myeloid Malignancy program's approved criteria, the main indications for referral were the diagnosis of AML or MDS at (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Min Fang, Mercy Laurino, Xiaoyu Qu, Kate Kroeger, Michele Beaumont, Natasha Carrera, Amanda Weatherford, Marshall Horwitz, Sio ḃán Keel Source Type: research
28. Analytical validation of an optical genome mapping assay for structural variant detection in hematologic malignancies
This study describes the validation of OGM as a laboratory developed test (LDT) for hematologic malignancies conducted at Bionano Laboratories. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - November 1, 2023 Category: Genetics & Stem Cells Authors: Trilochan Sahoo, Karena Kosco, Andy Wing Chun Pang, Jen Hauenstein, Beth Matthews, Anusha Mylavarapu, Julia Brushett, Alex Hastie, Alka Chaubey Source Type: research
