590 results match your criteria rearrangements interpretation


Epithelioid Fibrous Histiocytoma With Chondroblastoma-Like Features: A Report of a Rare Entity and Discussion of Related Diagnostic Challenges.

Am J Dermatopathol 2021 Jun 2. Epub 2021 Jun 2.

Department of Pathology and Laboratory Medicine, Nova Scotia Health Authority (Central Zone), Halifax, NS, Canada; Department of Ophthalmology, Nova Scotia Health Authority (Central Zone), Halifax, NS, Canada; Departments of Ophthalmology and Visual Sciences, Pathology, and; Medicine, Dalhousie University, Halifax, NS, Canada; and Department of Pathology and Laboratory Medicine, Nova Scotia Health Authority (Western Zone), Kentville, NS, Canada.

Abstract: Epithelioid fibrous histiocytoma (EFH) is an uncommon benign skin lesion. It is distinct from FH by virtue of its recurrent anaplastic lymphoma kinase (ALK) gene rearrangements and immunohistochemical expression of ALK protein. It often poses a challenge in interpretation. Read More

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Diagnostic validation of a clinical laboratory-oriented targeted RNA sequencing system for detecting gene fusions in hematologic malignancies.

J Mol Diagn 2021 May 31. Epub 2021 May 31.

Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun; Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address:

Targeted RNA sequencing (RNA-seq) is a highly accurate method for sequencing transcripts of interest with a high resolution and throughput. However, RNA-seq has not been widely performed in clinical molecular laboratories due to the complexity of data processing and interpretation. We developed and validated a customized RNA-seq panel and data processing protocol for fusion detection using four analytical validation samples and 51 clinical samples, covering seven types of hematologic malignancies. Read More

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Multiple immunoglobulin kappa rearrangements within a single clone unraveled by NGS-based clonality assessment.

J Mol Diagn 2021 May 18. Epub 2021 May 18.

Department of Pathology, Radboud University Medical Centre Nijmegen, Geert Grooteplein Zuid 10, P.O Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address:

Clonality assessment of the immunoglobulin heavy (IGH) and light chain (IGK) using GeneScan analysis is an important supplementary assay in lymphoma diagnostics. Occasionally cases are encountered with an IGK rearrangement pattern that cannot readily be assigned to a monoclonal lymphoma, whereas the occurrence of bi-clonal lymphomas is rare and the result of the IGH locus of these cases is in line with monoclonality. We subjected three such ambiguous cases to next generation sequencing (NGS)-based clonality assessment. Read More

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Congenital chromoanagenesis in the routine postnatal chromosomal microarray analyses.

Am J Med Genet A 2021 May 14. Epub 2021 May 14.

The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.

Chromosomal microarray analyses (CMA) have greatly increased both the yield and diagnostic accuracy of postnatal analysis; it has been used as a first-tier cytogenetic test in patients with intellectual disability, autism spectrum disorder, and multiple congenital abnormalities. During the last 15 years, we performed CMA in approximately 8,000 patients with neurodevelopmental and/or congenital disorders, of which 13 (0.16%) genetically catastrophic complex chromosomal rearrangements were identified. Read More

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Modeling the evolutionary architectures of transcribed human enhancer sequences reveals distinct origins, functions, and associations with human-trait variation.

Mol Biol Evol 2021 May 10. Epub 2021 May 10.

Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.

Motivation: Despite the importance of gene regulatory enhancers in human biology and evolution, we lack a comprehensive model of enhancer evolution and function. This substantially limits our understanding of the genetic basis of species divergence and our ability to interpret the effects of non-coding variants on human traits.

Results: To explore enhancer sequence evolution and its relationship to regulatory function, we traced the evolutionary origins of transcribed human enhancer sequences with activity across diverse tissues and cellular contexts from the FANTOM5 consortium. Read More

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Molecular diagnosis in non-small-cell lung cancer: expert opinion on and testing.

J Clin Pathol 2021 Apr 19. Epub 2021 Apr 19.

Department of Pathology, Hospital Universitario Virgen del Rocío, Sevilla, Spain.

The effectiveness of targeted therapies with tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) depends on the accurate determination of the genomic status of the tumour. For this reason, molecular analyses to detect genetic rearrangements in some genes (ie, , , ) have become standard in patients with advanced disease. Since immunohistochemistry is easier to implement and interpret, it is normally used as the screening procedure, while fluorescence in situ hybridisation (FISH) is used to confirm the rearrangement and decide on ambiguous immunostainings. Read More

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Fusion proteins in lung cancer: addressing diagnostic problems for deciding therapy.

Expert Rev Anticancer Ther 2021 Mar 30:1-14. Epub 2021 Mar 30.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.

: Gene fusions are frequent chromosomal aberrations in solid tumors. In Lung cancer (LC) several druggable-fusions involving tyrosine kinase receptor genes have been described, including ALK, ROS1, RET and NTRK. In non-small cell lung cancer, testing for targetable fusions has become a part of routine clinical practice, greatly impacting therapeutic choice for patients with these aberrations. Read More

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High-resolution coded aperture optimization for super-resolved compressive x-ray cone-beam computed tomography.

Appl Opt 2021 Feb;60(4):959-970

Compressive x-ray cone-beam computed tomography (CBCT) approaches rely on coded apertures (CA) along multiple view angles to block a portion of the x-ray energy traveling towards the detectors. Previous work has shown that designing CA patterns yields improved images. Most designs, however, are focused on multi-shot fan-beam (FB) systems, handling a 1:1 ratio between CA features and detector elements. Read More

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February 2021

Evaluation of a worldwide EQA scheme for complex clonality analysis of clinical lymphoproliferative cases demonstrates a learning effect.

Virchows Arch 2021 Mar 8. Epub 2021 Mar 8.

Department of Pathology, Radboud University Medical Centre Nijmegen, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, The Netherlands.

Clonality analysis of immunoglobulin (IG) or T-cell receptor (TR) gene rearrangements is routine practice to assist diagnosis of lymphoid malignancies. Participation in external quality assessment (EQA) aids laboratories in identifying systematic shortcomings. The aim of this study was to evaluate laboratories' improvement in IG/TR analysis and interpretation during five EQA rounds between 2014 and 2018. Read More

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Local Laboratory Testing of Germline BRCA Mutations vs. Myriad: A Single-Institution Experience in Korea.

Diagnostics (Basel) 2021 Feb 22;11(2). Epub 2021 Feb 22.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Genetic diagnosis for human epidermal growth factor receptor 2-negative metastatic breast cancer patients with the germline (gBRCA) mutation has been emphasized since the development of polyadenosine diphosphate-ribose polymerase inhibitors. Myriad Genetics, Inc.'s (Salt Lake City, UT, USA) companion diagnostics service is almost exclusively used for genetic testing. Read More

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February 2021

On the role of hydrogen-bond exchanges in the spectral diffusion of water.

J Chem Phys 2021 Feb;154(6):064501

Department of Chemistry, University of Kansas, Lawrence, Kansas 66045, USA.

The dynamics of a vibrational frequency in a condensed phase environment, i.e., the spectral diffusion, has attracted considerable interest over the last two decades. Read More

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February 2021

Early prenatal diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins due to a 16q24.1 deletion.

Am J Med Genet A 2021 05 31;185(5):1494-1497. Epub 2021 Jan 31.

Laboratoire de Cytogénétique, Service d'Histologie-Embryologie-Cytogénétique, Hôpital Antoine Béclère, AP-HP Université Paris Saclay, Clamart, France.

First trimester ultrasound screening is an essential fetal examination performed generally at 11-13 weeks of gestation (WG). However, it does not allow for an accurate description of all fetal organs, partly due to their development in progress. Meanwhile, increased nuchal translucency (INT) is a widely used marker known to be associated with chromosomal deleterious rearrangements. Read More

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How I investigate minimal residual disease in acute lymphoblastic leukemia.

Int J Lab Hematol 2021 Jun 10;43(3):354-363. Epub 2021 Jan 10.

Clinical Pathology Laboratory, Flow Cytometry Division, Hospital Israelita Albert Einstein, São Paulo, Brazil.

Minimal Residual Disease (MRD) is the most important independent prognostic factor in acute lymphoblastic leukemia (ALL) and refers to the deep level of measurable disease in cases with complete remission by conventional pathologic analysis, especially by cytomorphology. MRD can be detected by multiparametric flow cytometry, molecular approaches such as quantitative polymerase chain reaction for immunoglobulin and T-cell receptor (IG/TR) gene rearrangements or fusion genes transcript, and high-throughput sequencing for IG/TR. Despite the proven clinical usefulness in detecting MRD, these methods have differences in sensitivity, specificity, applicability, turnaround time and cost. Read More

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NRG1 fusions in breast cancer.

Breast Cancer Res 2021 Jan 7;23(1). Epub 2021 Jan 7.

Hutchison-MRC Research Centre, University of Cambridge, Cambridge, CB2 0XZ, UK.

Background: NRG1 gene fusions may be clinically actionable, since cancers carrying the fusion transcripts can be sensitive to tyrosine kinase inhibitors. The NRG1 gene encodes ligands for the HER2(ERBB2)-ERBB3 heterodimeric receptor tyrosine kinase, and the gene fusions are thought to lead to autocrine stimulation of the receptor. The NRG1 fusion expressed in the breast cancer cell line MDA-MB-175 serves as a model example of such fusions, showing the proposed autocrine loop and exceptional drug sensitivity. Read More

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January 2021

Resolving Breakpoints of Chromosomal Rearrangements at the Nucleotide Level Using Sanger Sequencing.

Curr Protoc Hum Genet 2020 12;108(1):e107

Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts.

Novel cytogenetic tools are increasingly based on genome sequencing for detecting chromosomal abnormalities. Different sequence-based techniques optimized for diagnosis of structural variants can be useful for narrowing down the localization of breakpoints of chromosomal abnormalities, but do not offer nucleotide resolution of breakpoints for proper interpretation of gene disruption. This protocol presents the characterization of structural variants at nucleotide resolution using Sanger sequencing after low-pass large-insert genome sequencing or other long-molecule methods. Read More

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December 2020

Unified Description of the Specific Heat of Ionic Bulk Materials Containing Nanoparticles.

ACS Nano 2021 Jan 21;15(1):563-574. Epub 2020 Dec 21.

Centre for Nanotechnology Research, VIT University, Vellore 632014, Tamil Nadu, India.

The specific heat behavior in bulk nanomaterials (NMs) obtained by adding nanoparticles to pure suspending media has attracted a lot interest in recent years. Controversial results about NMs specific heat () have been reported in the literature, where nanoparticles (NPs) of different sizes and materials were suspended in solid and liquid salts at different concentrations and temperatures. However, a unified picture explaining the enhancements and diminutions by adding NPs to pure salts is still missing. Read More

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January 2021

Identification of EWSR1-NFATC2 fusion in simple bone cysts.

Histopathology 2021 May 16;78(6):849-856. Epub 2021 Mar 16.

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Aims: Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. Read More

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Validation and interpretation of IGH and TCR clonality testing by Ion Torrent S5 NGS for diagnosis and disease monitoring in B and T cell cancers.

Pract Lab Med 2020 Nov 25;22:e00191. Epub 2020 Nov 25.

Washington University School of Medicine, St. Louis, MO, USA.

Cancers of B and T lymphocytes are the most common hematologic malignancies in the US. Molecular assays for assessing clonal rearrangements of the immunoglobulin receptor (IGH) and T-cell receptor (TCR), commonly referred to as B- and T-cell clonality, as well as determination of IGH somatic mutation status, enables improved diagnostic accuracy and disease monitoring. Here we describe validation of NGS LymphoTrack (IGH, TCRG, Invivoscribe, Inc) with Ion Torrent S5 sequencing, which employs a different sequencing chemistry and has not been previously reported for NGS clonality to our knowledge. Read More

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November 2020

Using Ion Mobility-Mass Spectrometry to Extract Physicochemical Enthalpic and Entropic Contributions from Synthetic Polymers.

J Am Soc Mass Spectrom 2021 Jan 3;32(1):330-339. Epub 2020 Dec 3.

Mass Spectrometry Laboratory, University of Liège, MolSys Research unit, Quartier Agora, Allée du Six Aout 11, B-4000 Liège, Belgium.

Ion mobility-mass spectrometry (IM-MS) experiments are mostly used hand in hand with computational chemistry to correlate mobility measurements to the shape of the ions. Recently, we developed an automatable method to fit IM data obtained with synthetic homopolymers (i.e. Read More

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January 2021

Monitoring MRD in ALL: Methodologies, technical aspects and optimal time points for measurement.

Semin Hematol 2020 07 20;57(3):142-148. Epub 2020 Jun 20.

UCL Cancer Institute, London, UK.

The accurate determination of minimal or measurable residual disease (MRD) during the early months of therapy in acute lymphoblastic leukemia is well established as the most important independent prognostic biomarker, predicting response to combination chemotherapy. Stratification based on MRD maximizes treatment effectiveness while minimizing adverse effects. Allele-specific real-time quantitative PCR of clone-defining immunoglobin/T-cell receptor gene rearrangements in the patients' leukemic clones and/or multiparametric flow cytometric tracking of leukemia-associated immunophenotypes are considered standard of care. Read More

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Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: causes, characteristics and clinical applications.

J Exp Clin Cancer Res 2020 Nov 30;39(1):267. Epub 2020 Nov 30.

Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, China.

Pancreatic cancer is one of the most malignant tumors worldwide, and pancreatic ductal adenocarcinoma is the most common type. In pancreatic cancer, glycolysis is the primary way energy is produced to maintain the proliferation, invasion, migration, and metastasis of cancer cells, even under normoxia. However, the potential molecular mechanism is still unknown. Read More

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November 2020

Potential Unreliability of Uncommon ALK, ROS1, and RET Genomic Breakpoints in Predicting the Efficacy of Targeted Therapy in NSCLC.

J Thorac Oncol 2021 03 26;16(3):404-418. Epub 2020 Nov 26.

Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address:

Introduction: Variable genomic breakpoints have been identified through the application of target-capture DNA next-generation sequencing (NGS) for ALK, ROS1, and RET fusion detection in NSCLC. We investigated whether ALK, ROS1, and RET genomic breakpoint location can predict matched targeted therapy efficacy.

Methods: NSCLCs were analyzed by DNA NGS, target-specific RNA NGS, whole-transcriptome sequencing, and immunohistochemistry. Read More

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Key Points to Consider When Studying RNA Remodeling by Proteins.

Methods Mol Biol 2021 ;2209:1-16

Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA.

Cellular RNAs depend on proteins for efficient folding to specific functional structures and for transitions between functional structures. This dependence arises from intrinsic properties of RNA structure. Specifically, RNAs possess stable local structure, largely in the form of helices, and there are abundant opportunities for RNAs to form alternative helices and tertiary contacts and therefore to populate alternative structures. Read More

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Speckle correlation as a monitor of X-ray free-electron laser induced crystal lattice deformation.

J Synchrotron Radiat 2020 Nov 9;27(Pt 6):1470-1476. Epub 2020 Oct 9.

Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.

X-ray free-electron lasers (X-FELs) present new opportunities to study ultrafast lattice dynamics in complex materials. While the unprecedented source brilliance enables high fidelity measurement of structural dynamics, it also raises experimental challenges related to the understanding and control of beam-induced irreversible structural changes in samples that can ultimately impact the interpretation of experimental results. This is also important for designing reliable high performance X-ray optical components. Read More

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November 2020

Pan-TRK Immunohistochemistry.

Arch Pathol Lab Med 2020 Oct 28. Epub 2020 Oct 28.

From Pathology and Laboratory of Therapeutic Targets, Hospital Universitario HM Sanchinarro, HMHospitales, CIBERONC, Madrid, Spain (Conde, Lopez-Rios).

Context.—: Food and Drug Administration-approved TRK inhibitors with impressive overall response rates are now available for patients with multiple cancer types that harbor NTRK rearrangements, yet the identification of NTRK fusions remains a difficult challenge. These alterations are highly recurrent in extremely rare malignancies or can be detected in exceedingly small subsets of common tumor types. Read More

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October 2020

Svpluscnv: analysis and visualization of complex structural variation data.

Bioinformatics 2020 Oct 14. Epub 2020 Oct 14.

Genetics and Genomics Sciences, Icahn School of Medicine, New York, USA.

Motivation: Despite widespread prevalence of somatic structural variations (SV) across most tumor types, understanding of their molecular implications often remains poor. SVs are extremely heterogeneous in size and complexity, hindering the interpretation of their pathogenic role. Tools integrating large SV datasets across platforms are required to fully characterize the cancer's somatic landscape. Read More

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October 2020

Pathogenicity reclassification of two BRCA1/BRCA2 exonic duplications after identification of genomic breakpoints and tandem orientation.

Cancer Genet 2020 10 11;248-249:18-24. Epub 2020 Sep 11.

Department of Genetics, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, Porto 4200-072, Portugal; Institute of Biomedical Sciences Abel Salazar, University of Porto, Largo Prof. Abel Salazar, Porto 4099-003, Portugal. Electronic address:

The genomic consequence and clinical interpretation of large duplications are difficult to infer without determining the location and orientation of the duplicated sequence. We aimed to characterize two intragenic duplications detected in two hereditary breast and ovarian cancer syndrome (HBOC) families, namely BRCA1 exon 4 to 6 and BRCA2 exon 17 to 18, previously detected by multiplex ligation probe amplification and initially classified as variants of unknown significance. Using long range PCR, with duplication-specific primers, we were able to ascertain the genomic breakpoints and observed that the two rearrangements occurred in tandem and in direct orientation. Read More

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October 2020

Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.

Lancet 2020 09 1;396(10254):839-852. Epub 2020 Sep 1.

City of Hope National Medical Center, Duarte, CA, USA.

Background: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas.

Methods: We did a seamless design study at 14 cancer centres in the USA. Read More

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September 2020

Interplay of the nuclear envelope with chromatin in physiology and pathology.

Nucleus 2020 12;11(1):205-218

Department of Biology and Biotechnology, Sapienza University of Rome , Rome, Italy.

The nuclear envelope compartmentalizes chromatin in eukaryotic cells. The main nuclear envelope components are lamins that associate with a panoply of factors, including the LEM domain proteins. The nuclear envelope of mammalian cells opens up during cell division. Read More

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December 2020