Paraganglioma (PGL) Tumors in Patients with Succinate Dehydrogenase-Related PCC–PGL Syndromes: a Clinicopathological and Molecular Analysis
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Genomic and Transcriptomic Alterations Associated with Drug Vulnerabilities and Prognosis in Adenocarcinoma at the Gastroesophageal Junction
ARTICLE https://doi.org/10.1038/s41467-020-19949-6 OPEN Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction Yuan Lin1,8, Yingying Luo 2,8, Yanxia Sun 2,8, Wenjia Guo 2,3,8, Xuan Zhao2,8, Yiyi Xi2, Yuling Ma 2, ✉ ✉ Mingming Shao2, Wen Tan2, Ge Gao 1,4 , Chen Wu 2,5,6 & Dongxin Lin2,5,7 1234567890():,; Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes, and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and tran- scriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy- number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prog- nostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies. 1 Beijing Advanced Innovation Center for Genomics (ICG), Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, China. 2 Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3 Cancer Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China. -
Charts Chart 1: Benign and Borderline Intracranial and CNS Tumors Chart
Charts Chart 1: Benign and Borderline Intracranial and CNS Tumors Chart Glial Tumor Neuronal and Neuronal‐ Ependymomas glial Neoplasms Subependymoma Subependymal Giant (9383/1) Cell Astrocytoma(9384/1) Myyppxopapillar y Desmoplastic Infantile Ependymoma Astrocytoma (9412/1) (9394/1) Chart 1: Benign and Borderline Intracranial and CNS Tumors Chart Glial Tumor Neuronal and Neuronal‐ Ependymomas glial Neoplasms Subependymoma Subependymal Giant (9383/1) Cell Astrocytoma(9384/1) Myyppxopapillar y Desmoplastic Infantile Ependymoma Astrocytoma (9412/1) (9394/1) Use this chart to code histology. The tree is arranged Chart Instructions: Neuroepithelial in descending order. Each branch is a histology group, starting at the top (9503) with the least specific terms and descending into more specific terms. Ependymal Embryonal Pineal Choro id plexus Neuronal and mixed Neuroblastic Glial Oligodendroglial tumors tumors tumors tumors neuronal-glial tumors tumors tumors tumors Pineoblastoma Ependymoma, Choroid plexus Olfactory neuroblastoma Oligodendroglioma NOS (9391) (9362) carcinoma Ganglioglioma, anaplastic (9522) NOS (9450) Oligodendroglioma (9390) (9505 Olfactory neurocytoma Ganglioglioma, malignant (()9521) anaplastic (()9451) Anasplastic ependymoma (9505) Olfactory neuroepithlioma Oligodendroblastoma (9392) (9523) (9460) Papillary ependymoma (9393) Glioma, NOS (9380) Supratentorial primitive Atypical EdEpendymo bltblastoma MdllMedulloep ithliithelioma Medulloblastoma neuroectodermal tumor tetratoid/rhabdoid (9392) (9501) (9470) (PNET) (9473) tumor -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Download Via Github on RNA-Seq and Chip-Seq Data Analysis and the University of And/Or Bioconductor [33–35, 38–40]
Kumka and Bauer BMC Genomics (2015) 16:895 DOI 10.1186/s12864-015-2162-4 RESEARCH ARTICLE Open Access Analysis of the FnrL regulon in Rhodobacter capsulatus reveals limited regulon overlap with orthologues from Rhodobacter sphaeroides and Escherichia coli Joseph E. Kumka and Carl E. Bauer* Abstract Background: FNR homologues constitute an important class of transcription factors that control a wide range of anaerobic physiological functions in a number of bacterial species. Since FNR homologues are some of the most pervasive transcription factors, an understanding of their involvement in regulating anaerobic gene expression in different species sheds light on evolutionary similarity and differences. To address this question, we used a combination of high throughput RNA-Seq and ChIP-Seq analysis to define the extent of the FnrL regulon in Rhodobacter capsulatus and related our results to that of FnrL in Rhodobacter sphaeroides and FNR in Escherichia coli. Results: Our RNA-seq results show that FnrL affects the expression of 807 genes, which accounts for over 20 % of the Rba. capsulatus genome. ChIP-seq results indicate that 42 of these genes are directly regulated by FnrL. Importantly, this includes genes involved in the synthesis of the anoxygenic photosystem. Similarly, FnrL in Rba. sphaeroides affects 24 % of its genome, however, only 171 genes are differentially expressed in common between two Rhodobacter species, suggesting significant divergence in regulation. Conclusions: We show that FnrL in Rba. capsulatus activates photosynthesis while in Rba. sphaeroides FnrL regulation reported to involve repression of the photosystem. This analysis highlights important differences in transcriptional control of photosynthetic events and other metabolic processes controlled by FnrL orthologues in closely related Rhodobacter species. -
About SDHD Gene Mutations
About SDHD Gene Mutations About Genes Recommendations Genes are in every cell in our bodies. Genes are made Knowing if you have an SDHD mutation can help you of DNA, which gives instructions to cells about how to grow manage your medical care. and work together. We have two copies of each gene in each cell—one from our mother and one from our father. When MEN AND WOMEN genes work right, they help stop cancer cells from developing. If you know you have an SDHD mutation, it is important If one copy of a gene has a mutation, it cannot function as it to find tumors early. It is also important to tell your doctor should. This increases the risk for certain cancers. that you have this mutation before any medical procedures. TheSDH genes have instructions for turning food into energy Recommendations may vary according to your age. and helping fix mistakes in DNA. The four genes involved are Ages 8-18: SDHA, SDHB, SDHC, and SDHD. If there is a mutation in one • MRI of the whole body every 2-3 years of these genes, it can cause cells to grow and divide too much. This • Neck MRI every 2-3 years can lead to tumors called paragangliomas and pheochromocytomas. These tumors are often benign (non-cancerous) but can be Adults: cancer and spread in some cases. This condition is called • PET/CT scan as your doctor recommends hereditary paraganglioma/pheochromocytoma syndrome. All ages: Paragangliomas and Pheochromocytomas • Physical exam every year with blood pressure check Paragangliomas (PGLs) are slow-growing tumors that develop • Blood test every year along nerves or blood vessels. -
Central Neurocytoma SNP Array Analyses, Subtel FISH, and Review
Pathology - Research and Practice 215 (2019) 152397 Contents lists available at ScienceDirect Pathology - Research and Practice journal homepage: www.elsevier.com/locate/prp Case report Central neurocytoma: SNP array analyses, subtel FISH, and review of the T literature Caroline Sandera,1, Marco Wallenborna,b,1, Vivian Pascal Brandtb, Peter Ahnertc, Vera Reuscheld, ⁎ Christan Eisenlöffele, Wolfgang Kruppa, Jürgen Meixensbergera, Heidrun Hollandb, a Dept. of Neurosurgery, University of Leipzig, Liebigstraße 26, 04103 Leipzig, Germany b Saxonian Incubator for Clinical Translation, University of Leipzig, Philipp-Rosenthal Str. 55, 04103 Leipzig, Germany c Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstraße 16-18, 04107 Leipzig, Germany d Dept. of Neuroradiology, University of Leipzig, Liebigstraße 22a, 04103 Leipzig, Germany e Dept. of Neuropathology, University of Leipzig, Liebigstraße 26, 04103 Leipzig, Germany ARTICLE INFO ABSTRACT Keywords: The central neurocytoma (CN) is a rare brain tumor with a frequency of 0.1-0.5% of all brain tumors. According Central neurocytoma to the World Health Organization classification, it is a benign grade II tumor with good prognosis. However, Cytogenetics some CN occur as histologically “atypical” variant, combined with increasing proliferation and poor clinical SNP array outcome. Detailed genetic knowledge could be helpful to characterize a potential atypical behavior in CN. Only FISH few publications on genetics of CN exist in the literature. Therefore, we performed cytogenetic analysis of an intraventricular neurocytoma WHO grade II in a 39-year-old male patient by use of genome-wide high-density single nucleotide polymorphism array (SNP array) and subtelomere FISH. Applying these techniques, we could detect known chromosomal aberrations and identified six not previously described chromosomal aberrations, gains of 1p36.33-p36.31, 2q37.1-q37.3, 6q27, 12p13.33-p13.31, 20q13.31-q13.33, and loss of 19p13.3-p12. -
A Case of Mushroom‑Shaped Anaplastic Oligodendroglioma Resembling Meningioma and Arteriovenous Malformation: Inadequacies of Diagnostic Imaging
EXPERIMENTAL AND THERAPEUTIC MEDICINE 10: 1499-1502, 2015 A case of mushroom‑shaped anaplastic oligodendroglioma resembling meningioma and arteriovenous malformation: Inadequacies of diagnostic imaging YAOLING LIU1,2, KANG YANG1, XU SUN1, XINYU LI1, MINGHAI WEI1, XIANG'EN SHI2, NINGWEI CHE1 and JIAN YIN1 1Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044; 2Department of Neurosurgery, Affiliated Fuxing Hospital, The Capital University of Medical Sciences, Beijing 100038, P.R. China Received December 29, 2014; Accepted June 29, 2015 DOI: 10.3892/etm.2015.2676 Abstract. Magnetic resonance imaging (MRI) is the most tomas (WHO IV) (2). The median survival times of patients widely discussed and clinically employed method for the with WHO II and WHO III oligodendrogliomas are 9.8 and differential diagnosis of oligodendrogliomas; however, 3.9 years, respectively (1,2), and 6.3 and 2.8 years, respec- MRI occasionally produces unclear results that can hinder tively, if mixed with astrocytes (3,4). Surgical excision and a definitive oligodendroglioma diagnosis. The present study postoperative adjuvant radiotherapy is the traditional therapy describes the case of a 34-year-old man that suffered from for oligodendroglioma; however, studies have observed that, headache and right upper‑extremity weakness for 2 months. among intracranial tumors, anaplastic oligodendrogliomas Based on the presurgical evaluation, it was suggested that the are particularly sensitive to chemotherapy, and the prognosis patient had a World Health Organization (WHO) grade II-II of patients treated with chemotherapy is more favorable glioma, meningioma or arteriovenous malformation (AVM), than that of patients treated with radiotherapy (5‑7). -
Crystal Structure of Bacterial Succinate:Quinone Oxidoreductase Flavoprotein Sdha in Complex with Its Assembly Factor Sdhe
Crystal structure of bacterial succinate:quinone oxidoreductase flavoprotein SdhA in complex with its assembly factor SdhE Megan J. Mahera,1, Anuradha S. Heratha, Saumya R. Udagedaraa, David A. Dougana, and Kaye N. Truscotta,1 aDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia Edited by Amy C. Rosenzweig, Northwestern University, Evanston, IL, and approved February 14, 2018 (received for review January 4, 2018) Succinate:quinone oxidoreductase (SQR) functions in energy me- quinol:FRD), respectively (13, 15). The importance of this protein tabolism, coupling the tricarboxylic acid cycle and electron transport family, in normal cellular metabolism, is manifested by the iden- chain in bacteria and mitochondria. The biogenesis of flavinylated tification of a mutation in human SDHAF2 (Gly78Arg), which is SdhA, the catalytic subunit of SQR, is assisted by a highly conserved linked to an inherited neuroendocrine disorder, PGL2 (10). Cur- assembly factor termed SdhE in bacteria via an unknown mecha- rently, however, the role of SdhE in flavinylation remains poorly nism. By using X-ray crystallography, we have solved the structure understood. To date, three different modes of action for SdhE/ of Escherichia coli SdhE in complex with SdhA to 2.15-Å resolution. Sdh5 have been proposed, suggesting that SdhE facilitates the Our structure shows that SdhE makes a direct interaction with the binding and delivery of FAD (13), acts as a chaperone for SdhA flavin adenine dinucleotide-linked residue His45 in SdhA and main- (10), or catalyzes the attachment of FAD (10). Moreover, the re- tains the capping domain of SdhA in an “open” conformation. -
The New WHO Classification of Brain Tumors and Molecular Profiling in the Diagnosis of Gliomas
The New WHO Classification of Brain Tumors and Molecular Profiling in the Diagnosis of Gliomas Aivi Nguyen, MD Neuropathology Fellow Division of Neuropathology Center for Personalized Diagnosis (CPD) Glial neoplasms – infiltrating gliomas Astrocytic tumors • Diffuse astrocytoma II • Anaplastic astrocytoma III • Glioblastoma • Giant cell glioblastoma IV • Gliosarcoma Oligodendroglial tumors • Oligodendroglioma II • Anaplastic oligodendroglioma III Oligoastrocytic tumors • Oligoastrocytoma II • Anaplastic oligoastrocytoma III Courtesy of Dr. Maria Martinez-Lage 2 2016 3 The 2016 WHO classification of tumours of the central nervous system Louis et al., Acta Neuropathologica 2016 4 Talk Outline Genetic, epigenetic and metabolic changes in gliomas • Mechanisms/tumor biology • Incorporation into daily practice and WHO classification Penn’s Center for Personalized Diagnostics • Tests performed • Results and observations to date Summary 5 The 2016 WHO classification of tumours of the central nervous system Louis et al., Acta Neuropathologica 2016 6 Mechanism of concurrent 1p and 19q chromosome loss in oligodendroglioma lost FUBP1 CIC Whole-arm translocation Griffin et al., Journal of Neuropathology and Experimental Neurology 2006 7 Oligodendroglioma: 1p19q co-deletion Since the 1990s Diagnostic Prognostic Predictive Li et al., Int J Clin Exp Pathol 2014 8 Mutations of Selected Genes in Glioma Subtypes GBM Astrocytoma Oligodendroglioma Oligoastrocytoma Killela et al., PNAS 2013 9 Escaping Senescence Telomerase reverse transcriptase gene -
Malignant CNS Solid Tumor Rules
Malignant CNS and Peripheral Nerves Equivalent Terms and Definitions C470-C479, C700, C701, C709, C710-C719, C720-C725, C728, C729, C751-C753 (Excludes lymphoma and leukemia M9590 – M9992 and Kaposi sarcoma M9140) Introduction Note 1: This section includes the following primary sites: Peripheral nerves C470-C479; cerebral meninges C700; spinal meninges C701; meninges NOS C709; brain C710-C719; spinal cord C720; cauda equina C721; olfactory nerve C722; optic nerve C723; acoustic nerve C724; cranial nerve NOS C725; overlapping lesion of brain and central nervous system C728; nervous system NOS C729; pituitary gland C751; craniopharyngeal duct C752; pineal gland C753. Note 2: Non-malignant intracranial and CNS tumors have a separate set of rules. Note 3: 2007 MPH Rules and 2018 Solid Tumor Rules are used based on date of diagnosis. • Tumors diagnosed 01/01/2007 through 12/31/2017: Use 2007 MPH Rules • Tumors diagnosed 01/01/2018 and later: Use 2018 Solid Tumor Rules • The original tumor diagnosed before 1/1/2018 and a subsequent tumor diagnosed 1/1/2018 or later in the same primary site: Use the 2018 Solid Tumor Rules. Note 4: There must be a histologic, cytologic, radiographic, or clinical diagnosis of a malignant neoplasm /3. Note 5: Tumors from a number of primary sites metastasize to the brain. Do not use these rules for tumors described as metastases; report metastatic tumors using the rules for that primary site. Note 6: Pilocytic astrocytoma/juvenile pilocytic astrocytoma is reportable in North America as a malignant neoplasm 9421/3. • See the Non-malignant CNS Rules when the primary site is optic nerve and the diagnosis is either optic glioma or pilocytic astrocytoma. -
Multiple Endocrine Neoplasia Type 2: an Overview Jessica Moline, MS1, and Charis Eng, MD, Phd1,2,3,4
GENETEST REVIEW Genetics in Medicine Multiple endocrine neoplasia type 2: An overview Jessica Moline, MS1, and Charis Eng, MD, PhD1,2,3,4 TABLE OF CONTENTS Clinical Description of MEN 2 .......................................................................755 Surveillance...................................................................................................760 Multiple endocrine neoplasia type 2A (OMIM# 171400) ....................756 Medullary thyroid carcinoma ................................................................760 Familial medullary thyroid carcinoma (OMIM# 155240).....................756 Pheochromocytoma ................................................................................760 Multiple endocrine neoplasia type 2B (OMIM# 162300) ....................756 Parathyroid adenoma or hyperplasia ...................................................761 Diagnosis and testing......................................................................................756 Hypoparathyroidism................................................................................761 Clinical diagnosis: MEN 2A........................................................................756 Agents/circumstances to avoid .................................................................761 Clinical diagnosis: FMTC ............................................................................756 Testing of relatives at risk...........................................................................761 Clinical diagnosis: MEN 2B ........................................................................756 -
Generated by SRI International Pathway Tools Version 25.0, Authors S
Authors: Pallavi Subhraveti Peter D Karp Ingrid Keseler An online version of this diagram is available at BioCyc.org. Biosynthetic pathways are positioned in the left of the cytoplasm, degradative pathways on the right, and reactions not assigned to any pathway are in the far right of the cytoplasm. Transporters and membrane proteins are shown on the membrane. Anamika Kothari Periplasmic (where appropriate) and extracellular reactions and proteins may also be shown. Pathways are colored according to their cellular function. Gcf_000442315Cyc: Rubellimicrobium thermophilum DSM 16684 Cellular Overview Connections between pathways are omitted for legibility. Ron Caspi lipid II (meso phosphate diaminopimelate sn-glycerol containing) phosphate dCTP 3-phosphate predicted ABC RS07495 RS12165 RS03605 transporter RS13105 of phosphate lipid II (meso dCTP sn-glycerol diaminopimelate phosphate 3-phosphate containing) phosphate Secondary Metabolite Degradation Storage Compound Biosynthesis Tetrapyrrole Biosynthesis Hormone Biosynthesis Aromatic Compound Aldehyde Degradation UDP-N-acetyl- Biosynthesis undecaprenyl- a mature (4R)-4-hydroxy- an L-glutamyl- a [protein]-L- queuosine at Macromolecule Modification myo-inositol degradation I α-D-glucosamine adenosylcobinamide a purine L-canavanine 5'-deoxyadenosine sec Metabolic Regulator Biosynthesis Amine and Polyamine Biosynthesis polyhydroxybutanoate biosynthesis siroheme biosynthesis methylglyoxal degradation I diphospho-N- peptidoglycan 2-oxoglutarate Gln β-isoaspartate glu position 34 ser a tRNA indole-3-acetate