Clinical exome sequencing identified POLB c.C1002A as a possible genetic cause in a family with hereditary cancer-predisposing syndrome
This study recruited a Chinese family with hereditary cancer-predisposing syndrome. To investigate the causative mutations, disease-associated exome sequencing was conducted using peripheral blood of three members with malignant disease. As a result, three variants (PLD2 c. C1951T, RAB3GAP1 c.A701G and POLB c.C1002A) came out to be the potential candidate pathogenic mutations, which were not reported before. Sanger sequencing was used to validate the candidate variant in seven healthy members of this family. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 26, 2020 Category: Genetics & Stem Cells Authors: Zhenxin Zhu, Jieshi Wang, Lisha Jiang, Ling Lin, Peng Meng, Jiangman Zhao, Qingping Cai Tags: Case report Source Type: research

Evolution of histomorphologic, cytogenetic, and genetic abnormalities in an untreated patient with MIRAGE syndrome
MIRAGE syndrome is a recently described, severe multisystem disorder presenting in the neonatal period, characterized by myelodysplasia, recurrent infections, growth restriction, adrenal insufficiency, genital abnormalities, and enteropathy [1, 2]. De novo gain of function mutations in the gene SAMD9 located on chromosome 7 cause MIRAGE syndrome [2]. Hematopoietic cells counter the anti-proliferative effect of SAMD9 mutational activation by acquiring somatic genetic alterations in the copy of chromosome 7 carrying the mutant SAMD9 allele (e.g. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 14, 2020 Category: Genetics & Stem Cells Authors: Stefan Rentas, Vinodh Pillai, Gerald B. Wertheim, Gozde T. Akgumus, Kim E. Nichols, Matthew A. Deardorff, Laura K. Conlin, Marilyn M. Li, Timothy S. Olson, Minjie Luo Tags: nOriginal Article Source Type: research

Alcohol consumption and risk of breast and ovarian cancer: a Mendelian randomization study
Alcohol consumption is an established risk factor for several health-related outcomes. A recent analysis of data on nearly 600,000 individuals has demonstrated that the association between alcohol intake and risk of all-cause mortality begins at consumption levels much lower than generally believed [1]. Alcohol use has also been linked to an increased risk of several cancers. A retrospective analysis aggregating data from invasive cancer cases among American adults aged ≥ 30 years has estimated alcohol intake as the third largest contributor to all cancer cases among women [2]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 11, 2020 Category: Genetics & Stem Cells Authors: Jingjing Zhu, Xia Jiang, Zheng Niu Tags: Original article Source Type: research

Generation and Characterization of the E µ-Irf8 mouse model
Chromosomal translocations are an integral part of cancer pathogenesis. In hematological malignancies, they play an outsized role and, as exemplified by the t(9;22) /BCR-ABL fusion, and t(15;17) /PML-RAR α fusion, these abnormalities can inform the disease biology, diagnosis and the development of rational therapies [1]. In mature B-cell malignancies, chromosomal translocation often lead to the juxtaposition of a “target” gene locus to the regulatory regions of the immunoglobulin heavy (IGH) or light chain loci [2]. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 2, 2020 Category: Genetics & Stem Cells Authors: Zhijun Qiu, Kenneth N. Holder, An-Ping Lin, Jamie Myers, Shoulei Jiang, Karla M. Gorena, Marsha C. Kinney, Ricardo C.T. Aguiar Tags: Original article Source Type: research

1. Germline EGFR variants over-represented in adolescent and young adult (AYA) females with adrenocortical carcinoma
Adrenocortical Carcinoma (ACT) is a rare endocrine tumor with poor overall prognosis and slight overrepresentation in females. In children, ACT is associated with inherited cancer syndromes with 50-80% of childhood ACT associated with TP53 germline mutations. ACT in adolescent and young adult (AYA) are rarely due to germline TP53, IGF2, PRKAR1A and, MEN1 variants. We analyzed exome sequencing data from 21 children (C, 39y) with ACT, and retained all pathogenic, likely pathogenic, and highly prioritized Variants of Uncertain Significance. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Sara Akhavanfard, Lamis Yehia, Roshan Padmanabhan, Todd Romigh, Ying Ni, Charis Eng Source Type: research

2. Large structural variations in inflammatory breast cancer identifies possible pathognomonic alterations
Inflammatory breast cancer (IBC) is a clinical diagnosis that spans all breast cancer clinical and molecular subtypes. The clinical course of IBC is associated with poorer outcomes than molecular subtype-matched non-IBC and represents an unmet need in breast cancer therapy. IBC is characterized by invasive dermal lymphatic tumor emboli resulting in erythema and edema of the breast. These features suggest a pathognomonic common molecular theme or alteration, which if identified and targeted, could help reduce the mortality related to this highly aggressive breast cancer type. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Justin Balko, Ann Hanna, Paula Gonzalez-Ericsson, Abigail Toren, Susan Opalenik, Melinda Sanders Source Type: research

3. Use of a targeted gene panel to inform treatment decisions for patients with AML
Introduction: Targeted sequencing panels interrogating multiple recurrently mutated genes are increasingly ordered by physicians treating hematologic malignancies. However, the pattern of usage and the impact of sequencing results on clinical care is not well described. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Erica K. Barnell, Kenneth F. Newcomer, Zachary L. Skidmore, Kilannin Krysiak, Sydney R. Anderson, David H. Spencer, Eric J. Duncavage, Malachi Griffith, Meagan A. Jacoby, Obi Griffith Source Type: research

4. Genetic analysis of acute lymphoblastic leukemia developed after treatment with lenalidomide for multiple myeloma
Introduction: Patients with multiple myeloma (MM) who are treated with lenalidomide maintenance therapy can be subsequently diagnosed with acute lymphoblastic leukemia (ALL). To describe the clonal dynamics of this transformation, we performed somatic and germline sequence analysis of six patients who developed Philadelphia chromosome-negative (Ph-negative) ALL after a primary diagnosis of MM while on/or after maintenance therapy with lenalidomide. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Erica Barnell, Zachary L. Skidmore, Katie M. Campbell, Malachi Griffith, Obi L. Griffith, Lukas D. Wartman Source Type: research

5. RNA-based fusion studies critically improves clinical management of acute leukemias
Detection or exclusion of an increasing number of structural variants has become crucial to achieve accurate diagnosis and appropriate risk stratification, particularly in patients with acute leukemia. While RNA-based anchored multiplex PCR (AMP) can be used to identify gene fusion transcripts without a priori knowledge of the expected findings, the clinical utility when applied in conjunction with traditional cytogenetics has not been comprehensively characterized. Herein we describe an inter-institutional analysis of gene fusion detection via AMP-based studies and traditional cytogenetics across an unselected cohort of 1...
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Leonardo Boiocchi, Paola Dal Cin, Jochen Lennerz, Adrian Dubuc, Valentina Nardi Source Type: research

6. Multiplexed-PCR based next generation sequencing assay for diagnosis of bladder carcinoma in urine specimens
Background: Urine cytology has a low sensitivity for diagnosis of high grade urothelial carcinoma. Bladder cancer harbors frequent coding mutations in TP53, FGFR3, RAS, and PIK3CA, in addition to TERT promoter mutations. The study evaluates the feasibility of a multiplexed-PCR based Next Generation sequencing (NGS) assay on urine samples for diagnosis and monitoring of bladder carcinoma. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Ijeuru Chikeka, Simon Sung, Mahesh Mansukhani Source Type: research

7. ROS1-GOPC gene fusion characterizes a minor subset of brain tumors
Brain tumors are the leading cause of cancer-related death in children and young adults. Molecular genetic/genomic characteristics subclassify brain tumors, which associate with different outcomes and identify pathways for therapeutic options. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Linda Cooley, Kwok Kam, Craig Horbinski, Madina Sukhanova, Melissa Gener, Kevin Ginn, Xinyan Lu Source Type: research

8. Integrating genomic and transcriptomic data to identify splice altering mutations across 35 cancer types
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 may have unidentified non-coding consequences. To address this issue, we created RegTools, an open-source software package that integrates variant calls from genomic data with evidence of expressed splice junctions from transcriptomic data to identify variants associated with aberrant splicing. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Kelsy Cotto, Yang-Yang Feng, Zachary Skidmore, Avinash Ramu, Jason Kunisaki, Donald Conrad, Yiing Lin, William Chapman, Ravindra Uppaluri, Ramaswamy Govindan, Obi Griffith, Malachi Griffith Source Type: research

9. Expansion of the CIViC data model for functional annotation of cancer variants
With clinical adoption of massively parallel sequencing into personalized cancer treatment, a bottleneck occurs during clinical interpretation of the large amount of variants seen in tumors, which requires curating an ever increasing pool of published studies. While some groups approach this problem by housing variant interpretations behind paywalls to support further curation, the Clinical Interpretations of Variants in Cancer database (CIViC, www.civicdb.org) employs crowdsourced curation and expert moderation within a fully open and free resource. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Arpad Danos, Kilannin Krysiak, Jason Saliba, Justin Guerra, Alex Wagner, Joshua McMichael, Susanna Kiwala, Adam Coffman, Erica Barnell, Nicholas Spies, Lana Sheta, Shahil Pema, Lynzey Kujan, Kaitlin Clark, Malachi Griffith, Obi Griffith Source Type: research

10. Uveal melanoma: The New Zealand perspective
Uveal melanoma (UM) is the most common intraocular malignancy. The incidence of UM is 10 cases per million per year in New Zealand (twice the US incidence). Treatment options include enucleation, plaque brachytherapy and localised radiotherapy. Despite successful treatment of the primary tumour, metastasis occurs in up to half of all patients. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Amanda Dixon-McIver, Gini Kumar, Catherine Han Source Type: research

11. ChromoSeq: WGS-based karyotyping for hematologic malignancies
Conventional cytogenetics are a diagnostic cornerstone for hematologic malignancies but have changed little over the past 50 years. Newer whole genome sequencing (WGS) methods can provide unbiased single-nucleotide resolution of all genomic variants. We sought to determine the clinical utility of ChromoSeq, a high-coverage WGS-based assay, compared to conventional cytogenetics in hematologic malignancies. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Eric Duncavage, Molly Schroeder, Roxanne Wilson, Scott Kruchowski, Matthew Bohannon, Shelly O'Laughlin, David Spencer Source Type: research

12. Genetic evaluation of CLL using SNP-array CGH: Comparison with retrospective FISH data in our institution.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Canada. Genetic evaluation can be done using conventional karyotyping, fluorescent in situ hybridization (FISH), genomic arrays, Sanger sequencing and next generation sequencing methods. FISH usually targets 17p and 11q deletions, associated with poor clinical outcome. For almost 2 years, our laboratory as transitioned from FISH to genomic arrays. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Fl échère Fortin, Sébastien Chénier Source Type: research

13. Bioinformatics and interpretation for clinical reporting of an integrated whole genome and transcriptome assay
Whole genome and transcriptome sequencing (WGTS) enables comprehensive detection of cancer genome variation from a single cancer specimen, however, clinical reporting of these assays is challenged by the need for significant computational infrastructure and breadth of genomic algorithms needed for analysis. Here, we report on the deployment of a clinical bioinformatics process for comprehensive genomic profiling of a patient's tumour. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Alexander Fortuna, Prisni Rath, Alberto Leon, Xuemei Luo, Yogi Sundaravadanam, Peter Ruzanov, Heather Armstrong, Dillan Cooke, Iain Bancarz, Andre Masella, Alexis Varsava, Kayla Marsh, Santiago Velez, Madhuran Thiagarajah, Lawrence Heisler, Bernard Lam, C Source Type: research

14. Characterizing response to checkpoint blockade treatment in mouse urothelial carcinoma model with scRNA
While checkpoint blockade treatment has been shown to be highly effective in various tumor types, effectiveness for urothelial carcinoma has been minimal. To examine how urothelial carcinoma responds to combined PD-L1 and CTLA-4 inhibition, we used single cell RNA sequencing along with whole genome, exome, and bulk RNA sequencing derived from a mouse model with three condition groups: control, checkpoint treatment (Atezolizumab and Ipilimumab), and checkpoint treatment with CD4 depletion. The cell line used for analysis is an organoid-based line developed by inducing invasive urothelial carcinoma in mice through exposure t...
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Sharon Freshour, Bryan Fisk, Matthew Mosior, Jennifer Bolzenius, Obi Griffith, Vivek Arora, Malachi Griffith Source Type: research

15. The good, the bad, and the ugly of SNP array testing for cutaneous melanocytic neoplasms
Cutaneous melanocytic neoplasms (CMNs) with ambiguous histologic features are diagnostically challenging for anatomic pathology practices. Ancillary genomic testing by SNP array can identify copy number abnormalities and allelic imbalances potentially associated with malignancy. We tested 445 formalin fixed, paraffin embedded CMNs by SNP array (OncoScan CNV Plus Assay, Thermo Fisher Scientific). Specimens were reviewed by a pathologist for acceptable amount and percentage of tumor cells. The reportable range included deletions> 1 megabase (Mb), duplications> 2 Mb, copy neutral loss of heterozygosity (cnLOH)> 10 Mb...
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Katherine Geiersbach, William Sukov, Robert Jenkins, Patricia Greipp, Daniel Van Dyke, Ross Rowsey, Ruifeng Guo, Kandelaria Rumilla, Lori Erickson, Thomas Flotte, Benamin Kipp Source Type: research

16. Clinical value of a novel culture medium for simultaneous growth of hematopoietic cell lineages for cytogenetic analysis
Hematopoietic malignancies, a leading cause of death in the US, derive from lymphoid (T-cell, B-cell, and plasma cell) and myeloid cell lines. In most clinical cases, the cytogeneticist selects the hematopoietic cell line(s) to culture based upon the oncologist's clinical suspicion, and the cultures are initiated immediately after specimen receipt. Present culture media for a given cell lineage require specific mitogens or growth factors to stimulate cell growth, which limits the ability to accurately determine disease status if the incorrect cell type is initially chosen. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Steven Gersen, Benjamin Legendre, Catie Wadyka, Ayman Mohamed Source Type: research

17. One test to rule them all? The utility of nanopore sequencing for variant detection in hematological malignancies
Genetic assessment of hematological malignancy samples typically involves karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA) and short read sequencing to detect clinically significant variants. In addition, specialized techniques, such as Bionano optical mapping or mate pair sequencing can define breakpoints of structural abnormalities and detect gene fusions. A single clinical test allowing for the detection of both large and small events in the same platform including exact genetic breakpoints would allow for more efficient and inexpensive patient care. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: William Glen, Robert Wilson, Iya Znoyko, Vishwajeeth Pasham, Brynn Levy, Min Fang, Daynna Wolff Source Type: research

18. Two distinct cell lines in one hepatoblastoma tissue block
The patient was a 4 year old male diagnosed with hepatoblastoma. DNA was extracted from paraffin embedded tumor sections and analyzed using the OncoScan CNV assay. Tissue from the same block was independently analyzed on the a targeted DNA hybrid capture NGS platform. Initial microarray results indicated a copy number gain at 1q32.1 (PIK3C2B, MDM4), copy number gains on Chromosome 20 and multiple regions of loss of heterozygosity. In contrast, data from the NGS assay indicated whole chromosome gains of 2, 5, 10 and 17 along with the copy number gain at 1q32.1 (PIK3C2B, MDM4). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Leslie Grimmett, Joanna Plunkitt, Tamara Restrepo, Alanna Church, Sanda Alexandrescu, Marian Harris Source Type: research

19. A customized targeted next-generation sequencing (NGS) panel for solid tumours: Analysis of the first 100 specimens
The aim of this study is to assess outcomes obtained on the first 105 samples using a customized solid tumour panel, covering hotspot regions in 31 genes. This 'Q31 assay' was recently implemented following a validation comprising of an amplicon-based QIAseq Targeted Panel, MiSeq, CLC Genomic Workbench for bioinformatics analysis and QCI-Interpret for variant interpretation and reporting. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Afia Hasnain, Shantanu Banerji, Ron Agatep, Tamara Dyck, Paul Park, Beth Spriggs Source Type: research

20. A resource for our clinical genomics community: The Compendium of Cancer Genome Aberrations (CCGA)
The Compendium of Cancer Genome Aberrations (CCGA, http://www.ccga.io) is a Cancer Genomics Consortium (CGC)-supported resource cataloging genomic/genetic abnormalities in neoplasia. This Wiki style interface promotes expert crowdsourcing, real-time editing and content sharing within our genomics community. The CCGA is intended to be a central hub of information with primary content plus direct links to pertinent literature and external databases for interpretation of molecular and cytogenetics cancer cases. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Jennelle C. Hodge, Beth Pitel, Brian Davis, Linda D. Cooley, Hui Chen, Scott Newman, Ying Zou, Kilannin Krysiak, Soheil Shams, Fei Yang, Malini Sathanoori, Fabiola Quintero-Rivera, Greg Corboy, Daynna J. Wolff Source Type: research

21. ctDx NSCLC assay: From diagnostic laboratory to patient care, development, validation, and clinical utility, case review
Lung cancer is the second most common cancer in both men and women. The American Cancer Society's estimates about 228,820 new cases of lung cancer and about 135,720 deaths from lung cancer in 2020. The clinical outcome of the lung cancer patients has markedly improved since the advent of molecular diagnostic tests having the evidence of clinical utility. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Seyed Ali Hosseini Source Type: research

22. Standard operating procedure for personalized cancer vaccine designs
Recent efforts to design personalized cancer immunotherapies use predicted neoantigens. To create a personalized cancer vaccine, strong-binding neoantigenic peptides are computationally predicted from matched tumor-normal sequencing data, and then ranked according to their predicted capability in stimulating a T cell response. These neoantigenic peptides arise due to various changes in the somatic genome and identification and characterization of these neoantigens is a critical step in designing these treatment regimens. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Jasreet Hundal, Susanna Kiwala, Huiming Xia, Megan Richters, Christopher Miller, Jason Walker, Elaine Mardis, William Gillanders, Obi Griffith, Malachi Griffith Source Type: research

23. Concurrent detection of CNVs and mutations using a myeloid malignancy NGS panel: Is it ready for prime time?
Aims: Genetic abnormalities including copy number variants (CNVs, gains and losses), and gene mutations are important for diagnostics and treatment of myeloid malignances. Somatic gene mutations can be detected by next generation sequencing (NGS), but CNVs are usually detected by karyotyping and fluorescence in situ hybridization (FISH). The aim of this proof-of-principle study was to investigate the feasibility of using the same NGS data to simultaneously detect both somatic mutations and CNVs. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Liqun Jiang, Aparna Pallavajjala, Jialing Huang, Laura Morsberger, Christopher Gocke, Ying Zou Source Type: research

24. Clinical considerations for migration between genome assemblies: Lessons learned in moving to GRCh38
Most bioinformatics applications depend on mapping genomic data to the reference genome sequence. The most commonly used human reference version is GRCh37 (hg19) has been around for eleven years, and is employed widely across both clinical and research applications. Some research labs and genomic databases have transitioned to the most recent GRCh38 (hg38), the successor of hg19, which became available in late 2013. However, clinical labs are taking longer to adopt the newer genome build and most labs still employ hg19. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Sabah Kadri, Andrew Skol Source Type: research

25. Importance of internal controls to monitor performance of sensitive qPCR JAK2 V617F test kits
The JAK2 V617F mutation is commonly detected in myeloproliferative neoplasms (MPN) accounting for>95% of cases of polycythemia vera and approximately 50% of cases of both essential thrombocythemia and primary myelofibrosis. JAK2 V617F mutation screening is routinely done to support a diagnosis of MPN and rule out other entities in the differential diagnosis. Sensitive, allele-specific quantitative PCR kits are available that can detect the V617F allele at (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Nathan Kopp, Celeste Eno, Niroshi Senaratne, Joshua Deignan, Thomas Lee Source Type: research

26. Community engagement for crowd-sourcing clinically relevant somatic variants, the CIViC experience.
The crowd-sourced, public domain knowledgebase CIViC (Clinical Interpretations of Variants in Cancer; civicdb.org) is composed of literature-derived evidence for the clinical utility of cancer variants. Evidence is captured in CIViC using concepts from established ontologies and CIViC-defined descriptive fields alongside human-readable text. This structured data allows for complex searches, programmatic access, and rapid integration into other resources. Anyone can curate evidence for CIViC by creating a login. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Kilannin Krysiak, Arpad Danos, Alex Wagner, Joshua McMichael, Adam Coffman, Susanna Kiwala, Nick Spies, Lynzey Kujan, Erica Barnell, Lana Sheta, Shahil Pema, Kaitlin Clark, Jason Saliba, Yang-Yang Feng, Benjamin Ainscough, Zach Skidmore, Cody Ramirez, Mal Source Type: research

27. Genome imaging of head and neck solid tumors: Oropharyngeal, tongue, and thyroid cancers
Large structural variants (SVs), such as insertions, deletions, and translocations are not readily detected using standard methods of whole genome analysis. Genome imaging using the Saphyr instrument from Bionano Genomics detects large (>500bp) and complex SVs that are difficult to detect using traditional short read sequencing alone. We have isolated high-molecular weight DNA (>150,000 bp) from various solid head and neck tumors using a nanobind disc, consisting of novel nano structured silica surrounding a paramagnetic disk. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Brandon LaBarge, Max Hennessy, Lijun Zhang, Kathryn Sheldon, David Goldenberg, James Broach Source Type: research

28. Next-generation sequencing as a tool for precision medicine in clinical oncology
Next-generation sequencing (NGS) has become the most effective tool in the practice of clinical oncology. The technology allows for rapid detection of variants in DNA/RNA simultaneously in a single run within a few days. The results provide valuable information on diagnostic, prognostic and therapeutic targets, which help physicians determine the treatment strategy for cancer patients. Using Ion Torrent S5 platform, we have implemented the Ion Torrent 52-gene Oncomine Focus Assay (OFA) for solid tumors and 74-gene Oncomine Myeloid Assay (OMA) for hematological malignancies as routine clinical practice. (Source: Cancer Gene...
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Xia Li, Guang Liu, Haigang Gu, Janet Orton Source Type: research

29. When amplification meets gene fusion: Molecular characterization of PPP1CB-ALK fusion and amplification in pediatric HGG
Anaplastic lymphoma kinase (ALK) is a well-known proto-oncogene. Different mechanisms leading to constitutively activated ALK protein have been reported, such as chromosomal rearrangements creating ligand-independent ALK chimeric protein and gene amplification resulting in overexpression of ALK. However, ALK rearrangement and amplification rarely co-exist in the same tumor. Here we report a high-grade glioma with PPP1CB-ALK fusion and amplification of the fusion gene. PPP1CB-ALK, which juxtaposed exon5 of PPP1CB with exon20 of ALK, and fusion gene amplification were identified by CHOP Comprehensive Solid Tumor Panel and co...
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Fumin Lin, Yiming Zhong, Feng Xu, Jeffery Schubert, Jinhua Wu, Xiaonan Zhao, Luanne Wainwright, Kajia Cao, Zhiqian Fan, Angela Viaene, Mariarita Santi, Adam Resnick, Phillip Storm, Marilyn Li Source Type: research

30. Curation of genetic variants in childhood cancers within the Clinical Genome Resource (ClinGen)
The Clinical Genome Resource (ClinGen) Somatic Cancer Clinical Domain Working Group (CDWG) (https://www.clinicalgenome.org/working-groups/somatic/) is a multi-institution team engaged in developing processes and resources to provide accurate curation and classification of somatic variants in cancer. While most knowledgebases provide information on variants in adult malignancies, alterations in pediatric cancers, which are fundamentally different, are rarely discussed. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Wan-Hsin Lin, Angshumoy Roy, Alanna Church, Shruti Rao, Deborah Ritter, Arpad Danos, Kilannin Krysiak, Laura Corson, Kevin Fisher, Heather Williams, Matthew Hiemenz, Katherine Janeway, Jianling Ji, Chimene Kesserwan, Theodore Laetsch, Donald Parsons, Ryan Source Type: research

31. Recurrent genomic alterations of chromosome 1q43q44 are diagnostic hallmarks in leiomyomas with bizarre nuclei
Leiomyomas (LMs) with bizarre nuclei are rare, clinically benign uterine smooth muscle tumors with atypical histologic features in young women. Although Fumarate Hydratase (FH) protein expression assay can further characterize them into LM-FH (Not expressed) and LM-BN (expressed) subtypes, the clinical diagnosis of LMs remain to be challenging due to limited assay sensitivity. We applied OncoScan SNP microarray analysis in 15 LM-FH and 5 LM-BN cases to understand the genomic landscape in LMs. Correlation with FH expression by immunohistochemistry (IHC) was performed. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Xinyan Lu, Tingting Gao, Madina Sukhanova, Brian S. Finkelman, Jianjun Wei Source Type: research

32. Genetic diagnosis of bone marrow failure syndromes: Strategies, yields, and challenges
Bone marrow failure syndromes (BMFS) are a group of heterogeneous disorders often associated with germline changes in pediatric patients, known as inherited BMFS (IBMFS). We developed an NGS panel interrogating 159 genes associated with IBMFS, which evaluates sequence and copy number variations. Testing can be ordered as a comprehensive panel or several sub-panels with reflex to a larger panel. A total of 236 patients were tested and a definitive or possible molecular diagnosis was found in 39 cases (16.5%) including 2 patients carrying two potential genetic etiologies. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Minjie Luo, Lea F. Surrey, Yiming Zhong, Daniel J. Gallo, Elizabeth H. Denenberg, Elizabeth A. Fanning, Fumin Lin, Xiaonan Zhao, Jinhua Wu, Jeffery Schubert, Kristin Zelley, Michele E. Paessler, Joseph H. Oved, Helge D. Hartung, Michele P. Lambert, Peter Source Type: research

33. Tumor testing of DNA repair genes in high grade serous ovarian cancer (HGSOC); a potential tool for personalized therapy
Ovarian cancer is the leading cause of death in women with gynecological tumors. Approximately 28% of women with high-grade serous ovarian cancer (HGSOC) carry either a germline or acquired somatic variant in BRCA1 or BRCA2 resulting in deficient homologous recombination repair (HRR). HRR deficiency may also be attributed to loss-of-function variants in other HRR pathway genes. Inhibitors of poly (ADP-ribose) polymerase (PARP inhibitors) are approved for HGSOC patients as first-line maintenance therapy in the presence of a BRCA loss-of-function variant which could be expanded to other HRR pathway genes as additional clinic...
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Elizabeth McCready, Darci Butcher, Crystal Woodside, Dorsa Kord, Mona Lisa Sur, Alice Lytwyn, Kathleen Bell, Landry Nfonsam, Coleman Choi, Daria Grafodatskaya Source Type: research

34. De novo constitutional PATRR-mediated t(3;8) balanced translocation associated with clear cell renal cell carcinoma
Our study describes a 33-year old male diagnosed with bilateral clear cell renal cell carcinoma (ccRCC) (8 primary tumors) who harbors a de novo constitutional Palindromic Adenine and Thymine Rich Repeat (PATRR)- mediated t(3;8) balanced translocation validated by spectral karyotyping. No germline or somatic pathogenic alterations were detected in VHL gene suggesting that his phenotype is not associated with Von Hippel-Lindau syndrome. Of note, there is no history of cancer in the family. We determined the chromosome 3 breakpoint to be located in an AT-rich palindromic sequence in the third intron of FHIT gene, member of t...
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Marilena Melas, Kevin J. McDonnell, Christopher Edlund, Sarah Correll Tash, Duveen Sturgeon, Charalampos Lazaris, Chenxu Qu, Peter J. Gruber, Thomas W. Glover, Beverly S. Emanuel, Stephen B. Gruber Source Type: research

35. Mosaicism as incidental finding in the pediatric next generation sequencing era
Rapidly emerging high throughput sequencing technology with higher depths of coverage increases the potential for unraveling genomic findings that are incidental to the initial indication for clinical testing. The interpretation and management of clinically meaningful incidental genomic findings is a pressing issue particularly in the pediatric population due to the impact of genetic information on the family and potential for additional clinical investigation. Our study describes a 16-month-old male with notable brain abnormalities, delayed visual maturation, microcephaly, global delay, growth deficiency, metopic craniosy...
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Marilena Melas, Mariam Mathew, Vijayakumar Jayaraman, Cortlandt Martin, Mari Mori, Amanda E. Jacobson-Kelly, Catherine Cottrell, Kristy Lee Source Type: research

36. Quadruple-hit B-cell lymphoma with simultaneous BCL2, BCL6, CCND1, and MYC rearrangements: Two new cases
The WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues has a section on high-grade B-cell lymphoma (HGBL) with MYC translocations, which includes double/triple-hit lymphomas characterized by MYC and BCL2 and/or BCL6 rearrangements, as well as other aggressive lymphomas without a MYC translocation that have a blastoid morphology or a morphology intermediate between DLBCL and BL (HGBL, NOS). 'Quadruple-hit' cases, defined by the presence of MYC, BCL2, BCL6, and CCND1 rearrangements, are rare; only three cases have been reported (1,2). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Aurelia Meloni-Ehrig, Zunyan Dai, Nathan Bohls, Michal Konarkowski, Patricia Stone, Martha Valenzuela, Alicia Tamayo, Zhenjun Lou, Kaye Siragusa, Dana Delgado, Catherine Li, Leilani Manera, Antonette Smith-Mitchell, Adrienne Kim, Claudia Kraemer, Stephani Source Type: research

37. Spatiotemporal patterns of metastatic spread and survival from MSK-IMPACT, a large-scale prospective clinical sequencing
Most large public cancer genomics datasets are focused on non-metastatic disease or lack information about spatiotemporal patterns of metastatic spread and survival. We have developed new clinical data extraction methods and performed an integrative analysis of clinical and genomic features from 34,836 patients treated at Memorial Sloan Kettering Cancer Center (MSK), stratified into 45 cancer subtypes. Tumors and matched normal were sequenced with MSK-IMPACT, a targeted next-generation sequencing assay that identifies genomic alterations in 468 genes. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Bastien Nguyen, Christopher Fong, Francisco Sanchez Vega, Anisha Luthra, Subhiksha Nandakumar, Henry Walch, Walid Chatila, Arjun Raj Rajanna, Renzo Dinatale, David Solit, Michael Berger, Ahmet Zehir, Jianjiong Gao, Nikolaus Schultz Source Type: research

38. Comparative molecular genomic analyses of a Rhesus Lynch Syndrome model
Colorectal cancer (CRC) is the third most common cancer in the U.S. Most CRC is sporadic, but Lynch Syndrome (LS) is the most common hereditary cancer syndrome predisposing to CRC and involves mismatch repair (MMR) deficiency. LS is secondary to germline mutations in one of four MMR genes (MLH1, MSH2, MSH6, and PMS2). Genetically engineered mouse models carrying germline mutations in MMR genes have significantly contributed to current understanding, but do not recapitulate the disease phenotype in LS patients and tissue-specific mouse models only do so partially. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Nejla Ozirmak Lermi, Stanton Gray, Muthuswamy Raveendran, Beth Dray, Ronald Harris, Fernando Benavides, Christian Abee, Jeffrey Rogers, Eduardo Vilar Source Type: research

39. Integrated informatics analysis of cancer-related variants with OpenCRAVAT
The modern researcher is confronted with hundreds of published methods to interpret genetic variants. There are databases of genes and variants, phenotype-genotype relationships, algorithms that score and rank genes, and computational tools for variant effect prediction. Because variant prioritization is a multifactorial problem, a welcome development in the field has been the emergence of decision support frameworks, which make it easier to integrate multiple resources in an interactive environment. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Kymberleigh Pagel, Rick Kim, Kyle Moad, Ben Busby, Lily Zheng, Collin Tolkheim, Michael Ryan, Rachel Karchin Source Type: research

40. Congenital Hemangioma: An unusual case as characterized by pathogenic GNA11 mutation
We report an unusual case of an infant who developed in utero multi-focal vascular tumors, suggestive of congenital hemangioma and exhibit spontaneous clinical involution. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Thuy Phung, Dolores Lopez-Terrada, Ionela Iacobas, Denise Metry Source Type: research

41. Somatic and mosaic mutations in the PI3-Kinase/Akt1 pathway in overgrowth syndromes
We describe three patients with overgrowth syndromes whose diagnosis was confirmed by demonstration of somatic and mosaic mutations in PI3-Kinase catalytic subunit alpha (PIK3CA) and Akt1. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Thuy Phung, Angshumoy Roy Source Type: research

42. Genomic gymnastics: Using RNAseq and mate pair sequencing to collaboratively decipher structural variation
Structural variation is integral to several mechanisms of oncogenicity, including gene fusions, tumor suppressor disruption, copy number variants (CNVs), and upregulation of oncogenes via position effects. The Mayo Clinic Genomics laboratory used clinically validated assays to perform RNA sequencing (RNAseq) and mate pair sequencing (MPseq) on 15 neoplastic specimens, including 8 hematologic and 7 solid tumor specimens. Conventional cytogenetic studies detected abnormalities in 10 of these cases, directing targeted analyses of NGS data. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Beth Pitel, Numrah Fadra, Jaime Davila, Patricia Greipp, Nicole Hoppman, Rory Jackson, Robert Jenkins, Sarah Johnson, Ivy Luoma, Kay Minn, Rohini Mopuri, Asha Nair, Kathryn Pearce, Jess Peterson, James Smadbeck, George Vasmatzis, Linda Baughn, Kevin Halli Source Type: research

43. PAX5 partial tandem duplication in pediatric B-ALL: Incidence and clinical, morphologic and genetic correlations
Gain of extra copies of the 5 ′ portion of the PAX5 gene (PAX5-partial tandem duplication or PAX5-PTD) has been proposed to define a specific genetic subgroup of B-ALL (PMID: 30842609), and has most recently been associated with the novel PAX5-alteration driven (PAX5alt) subtype of the disease (PMID: 30643249). We determined t he incidence and clinical, morphologic and molecular correlations of PAX5-PTD in an unselected cohort of 228 B-ALL patients. PAX5-PTD was detected by Chromosomal microarray (CMA) analysis in 5/228 B-ALLs (2.1%). (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Gordana Raca, Matthew Oberley, Le Aye, Andrew Doan, Jianling Ji, Ryan Schmidt, Jaclyn Biegel, Deepa Bhojwani Source Type: research

44. Karyotype and cytogenomic analysis essential in interpreting Xp-ter trisomy in a female infant with multiple anomalies
A late preterm female infant presented to the NICU with IUGR, hypoglycemia, hypotonia, a VSD, poor postnatal growth, feeding intolerance, and dysmorphic craniofacial features. Microarray analysis identified a 23.7 Mb duplication of the Xp22.33p22.11 region. The karyotype was found to be 46,XX, der(11)t(X;11)(p22.1p15.5)dn. Telomere-associated repeat FISH confirmed that both the 11p and Xp telomere regions were intact on the p arm of the derivative chromosome as well as on the normal chromosome 11 and both normal X chromosomes. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Ramakrishnan Sasi, Rebecca Burke, Jamie Senft, Michelle Spruill, Peter Perrotta Source Type: research

45. Identification of predicted neoantigen vaccine candidates in follicular lymphoma patients
There is a need for new follicular lymphoma (FL) therapies without long-term complications of chemotherapy and with curative potential. We hypothesize that FL contains tumor-specific mutant antigens (TSMAs) that can be targeted by the immune system by vaccination. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Cody Ramirez, Felix Frenkel, Olga Plotnikova, Vladislav Belousov, Alexander Bagaev, Elena Ocheredko, Susanna Kiwala, Jasreet Hundal, Zachary Skidmore, Marcus Watkins, Michelle Becker-Hapak, Thomas Mooney, Jason Walker, Catrina Fronick, Robert Fulton, Robe Source Type: research

46. ClinGen somatic cancer working group: Enhancing standardized interpretation of cancer genetic data for clinical use
The Clinical Genome (ClinGen) Resource, is a US National Human Genome Research Institute (NHGRI)-funded program to facilitate interpretation, annotation and utilization of clinical genomic data. ClinGen assembles experts to engage in standardized curation within clinical domains. Somatic Cancer is a ClinGen Clinical Domain Working Group (CDWG), consisting of>95 members worldwide with clinical (oncology, pathology) and genomics expertise. Somatic CDWG members identify cancer candidate genes that require expert curation to achieve consensus in clinical interpretation. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - June 1, 2020 Category: Genetics & Stem Cells Authors: Shruti Rao, Deborah Ritter, Arpad Danos, Gordana Raca, Angshumoy Roy, Kilannin Krysiak, Wan-Hsin Lin, Erica Barnell, Matthew McCoy, Beth Pitel, Dmitriy Sonkin, Jue Wang, Seyed Ali Hosseini, Shamini Selvarajah, Ian King, Rashmi Kanagal-Shamana, Xinjie Xu, Source Type: research