A Reappraisal of Superficial Pleomorphic Liposarcoma

2020 ◽  
Vol 154 (3) ◽  
pp. 353-361
Author(s):  
Scott Hilliard Berg ◽  
Cathy Meade Massoud ◽  
Colleen Jackson-Cook ◽  
Sosipatros Alexander Boikos ◽  
Steven Christopher Smith ◽  
...  
Keyword(s):  
Genetic Alterations ◽  
Pleomorphic Liposarcoma ◽  
Genomic Changes ◽  
Snp Microarray ◽  
Genome Wide ◽  
Genetic Features ◽  
Atypical Cells ◽  
Microarray Studies ◽  
Gains And Losses

Abstract Objectives Superficial pleomorphic liposarcoma (PL) has a favorable prognosis compared to deeply seated PL. Given developments in the classification of lipomatous neoplasms, we reappraised a series of cases. Methods Retrospective clinicopathologic evaluation and genome-wide single-nucleotide polymorphism (SNP) microarray studies were performed for cases previously designated superficial PL. Results Four cases were identified (age, 48-70 years). Two were dermally confined, whereas two were superficial subcutaneous; no recurrences or metastases were reported. Tumors demonstrated pleomorphic spindled morphology with variable cellularity. Multivacuolated atypical lipoblasts were focal in 3 and abundant in 1. Dermal tumors demonstrated atypical cells within sclerotic collagen. Genome-wide SNP microarray studies revealed consistent gains and losses, including losses at the 13q14.2 locus encompassing RB1 and DLEU2 and deletion/disruption of the TP53 locus. Although subcutaneous examples showed genomic changes similar to deep PL, the dermal examples showed fewer genetic alterations, including changes reported in the spectrum of atypical spindle cell/pleomorphic lipomatous tumors (ASPLT). All lacked MDM2 amplification. Conclusions Careful integration of histologic and genetic features may improve classification of lipomatous neoplasms with atypia, allowing reclassification of some superficial PL as ASPLT.

scholarly journals Genome-Wide Mapping and Subtype Classification of Long Non-Coding RNA in Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2355-2355
Author(s):  
Rong Chen ◽  
Gabriel G Malouf ◽  
Jianping Zhang ◽  
Xuelin Huang ◽  
John N Weinstein ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Genetic Alterations ◽  
Cell Physiology ◽  
Fusion Transcripts ◽  
Subtype Classification ◽  
Genome Wide ◽  
Acute Myeloid

Abstract Background: Most efforts to characterize acute myeloid leukemia (AML) have focused so far on genetic and epigenetic aberrations, which can ultimately lead to altered protein-coding gene function. The roles of long non-coding RNAs (lncRNAs), which orchestrate cell physiology and act as key regulators of the AML oncogenic state, remain uncharacterized globally. Material and Methods: We performed a genomic analysis of GENCODE lncRNAs in 179 clinically annotated cases of de novo AML, using The Cancer Genome Atlas (TCGA) RNA-Seq data. In addition, we described global correlations between lncRNAs and the expression of cis- and trans-acting genes. We also established lncRNA-based subtype classification based on distinct signatures and then correlated that classification with fusion transcripts and genetic alterations. Results: Using stringent criteria (RPKM ≥1 in at least 10% of AML), we identified 2,913 expressed lncRNAs and used an integrative analysis to predict those that are potential regulators of AML oncogenic state. The expression of 1,935 (66.4%) lncRNAs showed positive correlations with the mRNA expression of their neighboring genes, while only 14 (0.4%) of the lncRNAs showed negative correlations. Gene ontology analysis using GREAT revealed enrichment of cis-neighboring genes in the PML body gene set (p=8.2x10-7). Unsupervised clustering of lncRNA-based expression showed five robust molecular clusters (C1 to C5), which were highly correlated with the mRNA-based classification. Of those, three clusters (C1, C2 and C5) were tightly associated with recurrent fusion transcripts; cluster C1 (n=16) was composed exclusively of promyelocytic leukemias, while cluster C5 (n=45) was enriched for MLL-rearranged cases (24.4%), and cluster C2 (n=31) was enriched for MYH11-CBFB or RUNX1-RUNX1T1 (55.2%) rearranged cases. Importantly, cluster C4 (n=30), which includes cytogenetically normal leukemias, was highly enriched for NPM1 (p=2.3x10-11) and FLT3 (p=1.6x10-4) mutations; conversely, cluster C3 (n=53) was highly enriched for recurrent copy-number alterations as well as RUNX1 (p=0.001) and TP53 somatic mutations (p=0.004). We further discovered a core of 37 lncRNAs significantly associated with a MLL-signature and 16 lncRNAs with a NPM1-mutated signature. Conclusion: This study describes the first genome-wide mapping and characterization of lncRNAs in AML and proposes a robust lncRNA-based classification. This classification may serve in defining core lncRNAs that orchestrate key oncogenic states in the different clinical subtypes. Disclosures No relevant conflicts of interest to declare.

scholarly journals Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 901 ◽  
Author(s):  
Asiya Gusa ◽  
Sue Jinks-Robertson
Keyword(s):  
Fungal Pathogens ◽  
Repetitive Sequences ◽  
Pathogenic Fungi ◽  
Genetic Alterations ◽  
Fungal Species ◽  
Chronic Infections ◽  
Yeast Saccharomyces Cerevisiae ◽  
Genomic Changes ◽  
Break Site ◽  
Repair Mechanisms

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models. Recent discoveries defining the role of sexual, parasexual, and unisexual cycles in the evolution of these pathogenic fungi further expanded our understanding of the diversity found in and between species. During mitotic growth, damage to DNA in the form of double-strand breaks (DSBs) is repaired, and genome integrity is restored by the homologous recombination and non-homologous end-joining pathways. In addition to faithful repair, these pathways can introduce minor sequence alterations at the break site or lead to more extensive genetic alterations that include loss of heterozygosity, inversions, duplications, deletions, and translocations. In particular, the prevalence of repetitive sequences in fungal genomes provides opportunities for structural rearrangements to be generated by non-allelic (ectopic) recombination. In this review, we describe DSB repair mechanisms and the types of resulting genome alterations that were documented in the model yeast Saccharomyces cerevisiae. The relevance of similar recombination events to stress- and drug-related adaptations and in generating species diversity are discussed for the human fungal pathogens Candida albicans and Cryptococcus neoformans.

scholarly journals The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilona E. Grabowicz ◽  
Bartek Wilczyński ◽  
Bożena Kamińska ◽  
Adria-Jaume Roura ◽  
Bartosz Wojtaś ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Genetic Alterations ◽  
Chromatin Organization ◽  
Open Chromatin ◽  
Low Grade ◽  
Strong Impact ◽  
Cell Matrix ◽  
Topologically Associating Domains ◽  
Genome Wide

AbstractGenome-wide studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different glioma types. We have recently created a unique atlas encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we intersected genome-wide atlas data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in WHO low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found the set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing specific glioma-related genes. Moreover, many genes associated with the cell–matrix adhesion Gene Ontology group, in particular 14 PROTOCADHERINs, were found to be regulated by long-range contacts with enhancers. Presented results demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy.

scholarly journals F-Box Genes in the Wheat Genome and Expression Profiling in Wheat at Different Developmental Stages

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1154
Author(s):  
Min Jeong Hong ◽  
Jin-Baek Kim ◽  
Yong Weon Seo ◽  
Dae Yeon Kim
Keyword(s):  
Developmental Stages ◽  
Brachypodium Distachyon ◽  
Triticum Aestivum L ◽  
Wheat Genome ◽  
Post Translational Modification ◽  
Genome Wide ◽  
A Genome ◽  
High Sequence Homology ◽  
Wide Scale

Genes of the F-box family play specific roles in protein degradation by post-translational modification in several biological processes, including flowering, the regulation of circadian rhythms, photomorphogenesis, seed development, leaf senescence, and hormone signaling. F-box genes have not been previously investigated on a genome-wide scale; however, the establishment of the wheat (Triticum aestivum L.) reference genome sequence enabled a genome-based examination of the F-box genes to be conducted in the present study. In total, 1796 F-box genes were detected in the wheat genome and classified into various subgroups based on their functional C-terminal domain. The F-box genes were distributed among 21 chromosomes and most showed high sequence homology with F-box genes located on the homoeologous chromosomes because of allohexaploidy in the wheat genome. Additionally, a synteny analysis of wheat F-box genes was conducted in rice and Brachypodium distachyon. Transcriptome analysis during various wheat developmental stages and expression analysis by quantitative real-time PCR revealed that some F-box genes were specifically expressed in the vegetative and/or seed developmental stages. A genome-based examination and classification of F-box genes provide an opportunity to elucidate the biological functions of F-box genes in wheat.

scholarly journals Authentication of Aspergillus parasiticus strains in the genome database of the National Center for Biotechnology Information

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Perng-Kuang Chang
Keyword(s):  
Aspergillus Parasiticus ◽  
Evolutionary Relationship ◽  
Cyclopiazonic Acid ◽  
Equivalent Strain ◽  
Nucleotide Polymorphisms ◽  
Genome Database ◽  
Single Nucleotide ◽  
Clonal Strain ◽  
Genome Wide ◽  
Genetic Features

Abstract Objective The use of genome sequences from strains authenticated to correct species level is a prerequisite for confidently exploring the evolutionary relationship among related species. Aspergillus strains erroneously curated as Aspergillus oryzae and Aspergillus fumigatus have been noticed in the National Center for Biotechnology Information (NCBI) genome database. Aspergillus parasiticus is one of several aspergilli that produce aflatoxin, the most potent carcinogenic mycotoxin known up to now. To ensure that valid conclusions are drawn by researchers from their genomics-related studies, molecular analyses were carried out to authenticate identities of A. parasiticus strains in the NCBI genome database. Results Two of the nine supposedly A. parasiticus strains, E1365 and NRRL2999, were found to be misidentified. They turned out to be Aspergillus flavus based on genome-wide single nucleotide polymorphisms (SNPs) and genetic features associated with production of aflatoxin and cyclopiazonic acid. NRRL2999 lacked the additional partial aflatoxin gene cluster known to be present in its equivalent strain, designated as SU-1, and shared a very low total SNPs count specifically with A. flavus NRRL3357 but not with other A. flavus isolates. Therefore, the mislabeled NRRL2999 strain actually is a clonal strain of A. flavus NRRL3357, whose genome was first sequenced in 2005.

scholarly journals Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322983
Author(s):  
Benjamin Goeppert ◽  
Damian Stichel ◽  
Reka Toth ◽  
Sarah Fritzsche ◽  
Moritz Anton Loeffler ◽  
...  
Keyword(s):  
Treatment Options ◽  
Genetic Alterations ◽  
Integrative Analysis ◽  
Intermediate Form ◽  
Precursor Lesions ◽  
Molecular Alterations ◽  
Genome Wide ◽  
Cells Of Origin ◽  
Sample Set ◽  
Methylation Profiling

ObjectiveA detailed understanding of the molecular alterations in different forms of cholangiocarcinogenesis is crucial for a better understanding of cholangiocarcinoma (CCA) and may pave the way to early diagnosis and better treatment options.DesignWe analysed a clinicopathologically well-characterised patient cohort (n=54) with high-grade intraductal papillary (IPNB) or tubulopapillary (ITPN) neoplastic precursor lesions of the biliary tract and correlated the results with an independent non-IPNB/ITPN associated CCA cohort (n=294). The triplet sample set of non-neoplastic biliary epithelium, precursor and invasive CCA was analysed by next generation sequencing, DNA copy number and genome-wide methylation profiling.ResultsPatients with invasive CCA arising from IPNB/ITPN had better prognosis than patients with CCA not associated with IPNB/ITPN. ITPN was localised mostly intrahepatic, whereas IPNB was mostly of extrahepatic origin. IPNB/ITPN were equally associated with small-duct and large-duct type intrahepatic CCA. IPNB exhibited mutational profiles of extrahepatic CCA, while ITPN had significantly fewer mutations. Most mutations were shared between precursor lesions and corresponding invasive CCA but ROBO2 mutations occurred exclusively in invasive CCA and CTNNB1 mutations were mainly present in precursor lesions. In addition, IPNB and ITPN differed in their DNA methylation profiles and analyses of latent methylation components suggested that IPNB and ITPN may have different cells-of-origin.ConclusionIntegrative analysis revealed that IPNB and ITPN harbour distinct early genetic alterations, IPNB are enriched in mutations typical for extrahepatic CCA, whereas ITPN exhibited few genetic alterations and showed distinct epigenetic profiles. In conclusion, IPNB/ITPN may represent a distinctive, intermediate form of intrahepatic and extrahepatic cholangiocarcinogenesis.

scholarly journals Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations

Blood ◽  
2012 ◽  
Vol 120 (10) ◽  
pp. 2076-2086 ◽  
Author(s):  
Britta Will ◽  
Li Zhou ◽  
Thomas O. Vogler ◽  
Susanna Ben-Neriah ◽  
Carolina Schinke ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Genetic Alterations ◽  
Fish Analysis ◽  
Exact Nature ◽  
Clinical Relapse ◽  
Hematopoietic Stem ◽  
Molecular Alterations ◽  
Genome Wide ◽  
Stem And Progenitor Cells ◽  
Specific Expansion

Abstract Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage−/CD34+/CD38−/CD90+) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% ± 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations.

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