Understand and explain equivalent fractions using visual models (4.NF.A.1) Glioblastomas are tumours that arise from astrocytes that comprise the supportive tissue of the brain. These tumours are usually aggressive as the cells divide rapidly and are also supported by a large network of blood vessels. The most aggressive subtype is glioblastoma multiforme (GBM) which is the most frequent form of brain cancer in adults, renowned for its lethality and poor prognosis and is thus an important target of study [132, 133].
Neurofibromin 1 (NF1) is a gene in humans that is located on chromosome 17. NF1 codes for neurofibromin, a GTPase-activating protein that negatively regulates RAS/MAPK pathway activity by accelerating the hydrolysis of Ras-bound GTP The frequency and nature of somatic NF1 mutations in different cancer types derived from the cBio dataset. a Malignant melanoma. b Lung adenocarcinoma. c Lung squamous cell carcinoma. d Small cell lung carcinoma. e Acute lymphocytic leukaemia (ALL). Acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), malignant myeloma (MM) and myelodysplastic syndrome (MDS). f Breast carcinoma. g Serous ovarian carcinoma. h Brain glioma, including glioblastoma multiforme (GBM). i Colorectal carcinoma. j Bladder transitional cell carcinoma. Mutations = single base-pair substitutions, in-frame microdeletions/insertions, frameshift microdeletions/insertions, splice site mutations (including those that can create in-frame deletions via exon skipping), nonsense mutations and frameshift insertions/deletions (shown in green); deletions = gross, multi-exonic and whole gene deletion identified as copy number changes (shown in blue); amplification = multi-exonic, whole gene duplications identified as copy number changes (shown in red); multiple alterations = some combination of mutations, deletions and/or amplification (shown in grey) [44,45,46]Peltonen S, Kallionpaa RA, Peltonen J. Neurofibromatosis type 1 (NF1) gene: beyond cafe au lait spots and dermal neurofibromas. Exp Dermatol. 2016. doi:10.1111/exd.13212. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Melanoma is a skin cancer that arises from melanocytes. Although the precise causes of melanomas are still not fully understood, environmental exposure to ultraviolet (UV) radiation from sunlight or tanning lamps certainly increases the risk of developing melanoma. Although NF1 is associated with pigmentary abnormalities such as CALMs, malignant melanoma is not a tumour type associated with NF1.
Seshagiri S, Stawiski EW, Durinck S, Modrusan Z, Storm EE, Conboy CB, Chaudhuri S, Guan Y, Janakiraman V, Jaiswal BS, et al. Recurrent R-spondin fusions in colon cancer. Nature. 2012;488(7413):660–4.This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. 1NF: 作为一个二维表，关系要符合一个最基本的田间，每个分量必须是不可分的数据项，即具有原子 1NF强调的是列的原子性，即列的属性不可再拆分。 比如下表包含「姓名」、「性别」、「电话」字..
There are three genes that are present within intron 27b of NF1. These genes are EVI2B, EVI2A and OMG, which are encoded on the opposite strand and are transcribed in the opposite direction of NF1. EVI2A and EVI2B are human homologs of the Evi-2A and Evi-2B genes in mice that encode proteins related to leukemia in mice. OMG is a membrane glycoprotein that is expressed in the human central nervous system during myelination of nerve cells. Taudin aiheuttavat mutaatiot neurofibromiini 1 (NF1)-geenissä, joka on kasvurajoitegeeni. Kahden tai useamman seuraavista diagnostisista kriteereistä on täytyttävä diagnoosin asettamiseks We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.T cell acute lymphoblastic leukaemia (T-ALL) is a variant of acute lymphoblastic leukaemia (ALL), with features similar to some types of lymphoma. It accounts for about 15 and 25% of ALL in paediatric and adult cohorts, respectively. *Vaikuttavat aineet, jotka ovat lääkevasteanalyysissa mukana alkoholi, amitriptyliini, arformoteroli, asenokumaroli, atatsanaviiri, atorvastatiini, atsatiopriini, belinostaatti, bosepreviiri, brivarasetaami, dabrafenibi, dapsoni, diatsepaami, diklofenaakki, doksepiini, dolutegraviiri, dronabinoli, efavirentsi, erlotinibi, esomepratsoli, essitalopraami, estradioli, etinyyliestradioli, fenprokumoni, fenytoiini, flibanseriini, fluorourasiili, flurbiprofeeni, fluvastatiini, fosfenytoiini, glibenklamidi, glimepiridi, glipitsidi, glyseryylitrinitraatti, hydroksiklorokiini, imipramiini, indakateroli, irbesartaani, irinotekaani, kapesitabiini, karisoprodoli, kiniini, klobatsaami, klomipramiini, klopidogreeli, klorokiini, kofeiini, lakosamidi, lansopratsoli, lesinuradi, losartaani, lovastatiini, merkaptopuriini, metyylitioniini, mivakurium, moklobemidi, nevirapiini, nilotinibi, nitrofurantoiini, omepratsoli, pantopratsoli, patsopanibi, peginterferoni alfa-2a, piroksikaami, prasugreeli, pravastatiini, primakiini, rabepratsoli, rasburikaasi, ribaviriini, romiplostiimi, rosuvastatiini, selekoksibi, sertraliini, simvastatiini, sisplatiini, suksametoni, sulfadiatsiini, sulfametoksatsoli, takrolimuusi, tamoksifeeni, tegafuuri, telapreviiri, tiboloni, tikagrelori, tioguaniini, trimipramiini, varfariini, vinkristiini, vorikonatsoli.
1NF1NIT1 - Player of Geometry Dash. Check his rank, stars, coins, levels and icons. 1. 1NF1NIT1 weekly progression Gutmann DH, Loehr A, Zhang Y, Kim J, Henkemeyer M, Cashen A. Haploinsufficiency for the neurofibromatosis 1 (NF1) tumor suppressor results in increased astrocyte proliferation. Oncogene. 1999;18(31):4450–9.Shilyansky C, Lee YS, Silva AJ. Molecular and cellular mechanisms of learning disabilities: a focus on NF1. Annu Rev Neurosci. 2010;33:221–43. Missense mutations found in NF1 patients map to NF1GRD, underscoring its importance for pathogenesis. X-ray crystallographic analysis of a proteolytically treated catalytic fragment of.. Ahmadian MR, Kiel C, Stege P, Scheffzek K. Structural fingerprints of the Ras-GTPase activating proteins neurofibromin and p120GAP. J Mol Biol. 2003;329(4):699–710.
See travel reviews, photos, videos, trips, and more contributed by @L10nf1sh on Tripadvisor. GenevaJoined in Sep 2009. L10nf1sh wrote a review Wu M, Wallace MR, Muir D. Nf1 haploinsufficiency augments angiogenesis. Oncogene. 2006;25(16):2297–303.Somatic NF1 mutations in neuroblastomas have been correlated with reduced expression of neurofibromin and poor patient prognosis, whilst higher levels of expression are associated with longer progression-free survival [130, 131]. Hölzel and colleagues also reported a loss of neurofibromin expression in 8/25 neuroblastoma cell lines and that a further SNP analysis of 20 neuroblastoma cell lines detected 50% (10/20) with abnormal NF1 alleles . Genomic aberrations in NF1 were also found in primary neuroblastomas but at a lower frequency of 6% (5/83).
Giannakis M, Mu XJ, Shukla SA, Qian ZR, Cohen O, Nishihara R, Bahl S, Cao Y, Amin-Mansour A, Yamauchi M, et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep. 2016;17(4):1206.Stenson PD, Mort M, Ball EV, Evans K, Hayden M, Heywood S, Hussain M, Phillips AD, Cooper DN. The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum Genet. 2017. doi:10.1007/s00439-017-1779-6 [Epub ahead of print].
Krauthammer M, Kong Y, Bacchiocchi A, Evans P, Pornputtapong N, Wu C, McCusker JP, Ma S, Cheng E, Straub R, et al. Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas. Nat Genet. 2015;47(9):996–1002.Welti S, D’Angelo I, Scheffzek K. Structure and function of neurofibromin. In: Neurofibromatoses. Basel: Karger; 2008:113–28. Shout @1NF1N1TY
. Comparative oncogenomics implicates the neurofibromin 1 gene (NF1) as a breast cancer driver. Genetics. 2012;192(2):385–96.JMML was once considered a unique example of RAS-driven oncogenesis because it was thought to be initiated by mutually exclusive mutations in the RAS genes (NRAS or KRAS) or in several RAS pathway regulators (PTPN11, NF1 or CBL) .Ding H, Shannon P, Lau N, Wu X, Roncari L, Baldwin RL, Takebayashi H, Nagy A, Gutmann DH, Guha A. Oligodendrogliomas result from the expression of an activated mutant epidermal growth factor receptor in a RAS transgenic mouse astrocytoma model. Cancer Res. 2003;63(5):1106–13.The NF1 gene is reported to be frequently mutated in sporadic breast cancers, although in only a few studies has mutation frequency been published. NF1 patients have an increased risk of developing breast cancer as compared to the general population [8, 98]. In particular, women under the age of 50 with NF1 have an increased (4–5-fold) risk of developing breast cancer (standardized incidence ratio for women under 50) and also a 3.5-fold increased fatality risk (proportionate mortality ratio) [98,99,100]. A predisposition to breast cancer in NF1 patients has led researchers to postulate the potential involvement of somatic NF1 mutations in initiating and driving the malignant transformation and progression of sporadic breast cancer. A number of breast cancer genome sequencing studies have identified NF1 as one of a number of novel, recurrently mutated genes in sporadic tumours which could potentially be targeted in a therapeutic context [101, 102].Through its NF1-GRD domain, neurofibromin increases the rate of GTP hydrolysis of Ras, and acts as a tumor suppressor by reducing Ras activity. When the Ras-Nf1 complex assembles, active Ras binds in a groove that is present in the neurofibromin catalytic domain. This binding occurs through Ras switch regions I and II, and an arginine finger present in neurofibromin. The interaction between Ras and neurofibromin causes GAP-stimulated hydrolysis of GTP to GDP. This process depends on the stabilization of residues in the Ras switch I and switch II regions, which drives Ras into the confirmation required for enzymatic function. This interaction between Ras and neurofibromin also requires the transition state of GDP hydrolysis to be stabilized, which is performed through the insertion of the positively charged arginine finger into the Ras active site. This neutralizes the negative charges that are present on GTP during phosphoryl transfer. By hydrolyzing GTP to GDP, neurofibromin inactivates Ras and therefore negatively regulates the Ras pathway, which controls the expression of genes involved in apoptosis, the cell cycle, cell differentiation or migration.
4X1nF 100Vdc 4X75 ohms. SHIELD. Green LED NF1是三星自己主導推廣的新介面SSD，目前支援NGSFF介面的廠商並不多，公開的只有三家：威剛 當然了，為了推廣NF1，即NGSFF介面的PM983，三星也推出了多種介面轉接卡： HHHL（半高全.. Brems H, Beert E, de Ravel T, Legius E. Mechanisms in the pathogenesis of malignant tumours in neurofibromatosis type 1. Lancet Oncol. 2009;10(5):508–15.The highest frequency of somatic NF1 mutations were found in desmoplastic melanomas (14/15) . These melanomas are characterized by their higher propensity for local recurrence and less frequent metastatic spread to regional lymph nodes. The high frequency of NF1 mutations in desmoplastic melanomas appears to indicate an important role for neurofibromin in the specific biology of this type of melanoma. Another recent study screened 20 desmoplastic melanomas by exome sequencing for alterations in the MAPK and PI3K signalling pathways, i.e. mutations in CBL, ERBB2, MAP2K1, MAP3K1, BRAF, EGFR, PTPN11, MET, RAC1, SOS2, NRAS and PIK3C, which were found in 15/20 (75%), with NF1 mutations being found in 9/20 (45%) .
NGSFF NF1 SSD In 1994, the first NF1 genetically engineered knockout mice were published: homozygosity for the Nf1 mutation (Nf1-/-) induced severe developmental cardiac abnormalities that led to embryonic lethality at early stages of the development, pointing out that NF1 plays a fundamental role in normal development. On the contrary, Nf1 heterozygous animals (Nf1+/-) were viable but predisposed to form different types of tumors. In some of these tumor cells, genetic events of loss of heterozygosity (LOH) were observed, supporting that NF1 functions as a tumor suppressor gene. A TCGA analysis assessed levels of gene expression, CNAs and DNA methylation in a cohort of 206 glioblastoma tumour samples, with recurrent mutations in NF1, AKT3, PRK3R1 and PARK2 being identified, and with 14% (13/91) of samples found to contain at least one somatic NF1 mutation. Verhaak and colleagues subsequently performed large-scale genomic analysis of these TCGA data, dividing glioblastoma cases into four subtypes: proneural, neural, classical and mesenchymal . They found that GBM with NF1 and PTEN alterations had a distinct mesenchymal-like expression profile, with 53% of mesenchymal cases having an NF1 mutation. The mutual exclusivity of NF1 and BRAF mutations in GBM has also been reported .. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214–8. doi:10.1038/nature12213.
Neurofibromatosis type 1 (NF1), formerly known as von Recklinghausen NF or Peripheral NF, is the While NF tumors are generally not cancerous, they may cause health problems by pressing on nearby.. The frequency of somatic NF1 mutations in different sporadic tumour types derived from the literature is given in Table 1. The cBioPortal for Cancer Genomics provides a web resource for exploring, visualizing and analysing multidimensional cancer genomics data and provides graphical summaries of gene-level data from multiple platforms, shown in Fig. 1 .
. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006;95 Suppl 1:S161–192.Deyell RJ, Attiyeh EF. Advances in the understanding of constitutional and somatic genomic alterations in neuroblastoma. Cancer Genet. 2011;204(3):113–21.Ahmadian MR, Wiesmuller L, Lautwein A, Bischoff FR, Wittinghofer A. Structural differences in the minimal catalytic domains of the GTPase-activating proteins p120GAP and neurofibromin. J Biol Chem. 1996;271(27):16409–15.Mautner VF, Kluwe L, Friedrich RE, Roehl AC, Bammert S, Hogel J, Spori H, Cooper DN, Kehrer-Sawatzki H. Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. J Med Genet. 2010;47(9):623–30.
Philpott, C., Tovell, H., Frayling, I.M. et al. The NF1 somatic mutational landscape in sporadic human cancers. Hum Genomics 11, 13 (2017). https://doi.org/10.1186/s40246-017-0109-3Johannessen CM, Reczek EE, James MF, Brems H, Legius E, Cichowski K. The NF1 tumor suppressor critically regulates TSC2 and mTOR. Proc Natl Acad Sci U S A. 2005;102(24):8573–8.The frequency of NF1 changes in myelodysplastic syndrome has been found to vary between 0 and 9% [86, 87].Large-scale NGS to compare primary and recurrent breast cancer has found mutations in recurrent tumours which were not present in matched primary tissue . However, the difficulties inherent in studying recurrent tumours mean that the sample size was necessarily small in this study, with only 74 matched tumours from 43 patients across the various breast cancer subtypes. So, the precise role for NF1 in breast cancer is still unclear and further studies are required.
Abdel-Wahab O, Tefferi A, Levine RL. Role of TET2 and ASXL1 mutations in the pathogenesis of myeloproliferative neoplasms. Hematol Oncol Clin North Am. 2012;26(5):1053–64.Cosgarea I, Ugurel S, Sucker A, Livingstone E, Zimmer L, Ziemer M, Utikal J, Mohr P, Pfeiffer C, Pfohler C, et al. Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations. Oncotarget. 2017.The new drive is built using 16 512-GB NAND packages, each of these being stacked in 16 layers of 256 Gb 3-bit V-NAND chips. The result is a data density of 8 TB in an 11 x 3.05 cm footprint. The M.2 NVMe solution currently used in ultra-slim laptops and server applications provides about half the storage for a size of 11 x 2.2 cm.
Sizi Tam 12'den Vuran Karakter Testleri, Ağzı Açıkta Bırakan Psikoloji Testleri, Genel Kültür Testleri, Zeka Testleri, IQ Testleri... Hepsi Onedio Test'te geenitestid.ee, Tallinn, Estonia. 3.1K likes. Teadmised oma geneetilistest iseärasustest aitavad tervislikumalt elada! Testi saad teha kodust lahkumata... Garcia-Orti L, Cristobal I, Cirauqui C, Guruceaga E, Marcotegui N, Calasanz MJ, Castello-Cros R, Odero MD. Integration of SNP and mRNA arrays with microRNA profiling reveals that MiR-370 is upregulated and targets NF1 in acute myeloid leukemia. PLoS One. 2012;7(10):e47717.
MODOR-NF-1m. Patchen mal anders gedacht. Der Autor gehört zu den Leuten, die gerne alles an Der MODOR NF-1m ist oberflächlich zwar ein Allround-Synthesizer, hat aber auf Grund seiner Filter.. Unicode web service for character search. Find, copy and paste your favorite characters: Emoji, Hearts, Currencies, → Arrows, Stars and many others..
The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many types of cells, including nerve cells and specialized cells called oligodendrocytes and Schwann cells that surround nerves. These specialized cells form myelin sheaths, which are the fatty coverings that insulate and protect certain nerve cells.Pasmant E, Sabbagh A, Spurlock G, Laurendeau I, Grillo E, Hamel MJ, Martin L, Barbarot S, Leheup B, Rodriguez D, et al. NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Hum Mutat. 2010;31(6):E1506–1518.
Cichowski K, Jacks T. NF1 tumor suppressor gene function: narrowing the GAP. Cell. 2001;104(4):593–604.Hollstein PE, Cichowski K. Identifying the ubiquitin ligase complex that regulates the NF1 tumor suppressor and Ras. Cancer Discov. 2013;3(8):880–93. - A Chave Push Button PBS-102 NF é um botão/pulsador utilizado comumente para dar ordem de acionamento em determinados projetos ou equipamentos ativados geralmente sempre que pulsados
In a recent study based on 2433 molecular profiles of breast cancer, it was noted that high levels of intra-tumour heterogeneity was generally associated with a worse clinical outcome, with one exception: highly aggressive breast tumours with 11q13–14 amplification had low levels of intra-tumour heterogeneity [108, 109]. Inactivating NF1 mutations were also found to be associated with breast cancer severity score in oestrogen receptor-negative tumours. Complete information for NF1 gene (Protein Coding), Neurofibromin 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium A large-scale analysis of a cohort of 202 paragangliomas and phaeochromocytomas, collected by the Cortico et Médullosurrénale: les Tumeurs Endocrines (COMETE) network, examined CNAs, somatic and constitutional mutations in known susceptibility genes . Almost a quarter (25/119) of the sporadic phaeochromocytomas/paragangliomas carried an inactivating NF1 mutation, of which 21/25 were associated with the loss of the wild-type allele. Of all the somatic mutations identified in the study, 56% were located in NF1, showing that NF1 is frequently mutated in phaeochromocytomas/paragangliomas .Jones DT, Hutter B, Jager N, Korshunov A, Kool M, Warnatz HJ, Zichner T, Lambert SR, Ryzhova M, Quang DA, et al. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat Genet. 2013;45(8):927–32.
Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTSUniProt annotationGO - Cellular componentNucleusNucleus 1 PublicationManual assertion based on experiment iniMore than a third of all ovarian serous carcinomas (OSCs) harbour somatic NF1 mutations, identifying an alternative target for treatment and an additional prognostic marker. This is of particular importance when considering the disease heterogeneity, high relapse and fatality rates [113, 114].Nissan MH, Pratilas CA, Jones AM, Ramirez R, Won H, Liu C, Tiwari S, Kong L, Hanrahan AJ, Yao Z, et al. Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence. Cancer Res. 2014;74(8):2340–50. Etusivu Keskustelualueet > Yleistä keskustelua >. Geenitesti Database Normalization 1NF, 2NF, 3NF, BCNF, 4NF, 5NF. 1. Normalization Oum Saokosal Master's Degree in Information Systems, South Korea 012-252-752 / 010-878-992 email@example.com 1
Akbani R, Ng PK, Werner HM, Shahmoradgoli M, Zhang F, Ju Z, Liu W, Yang JY, Yoshihara K, Li J, et al. A pan-cancer proteomic perspective on The Cancer Genome Atlas. Nat Commun. 2014;5:3887.Foster WJ, Fuller CE, Perry A, Harbour JW. Status of the NF1 tumor suppressor locus in uveal melanoma. Arch Ophthalmol. 2003;121(9):1311–5. CCLS - Math: 4.NF.1. Math Studio Talk: Common Core Instruction for 4.NF. Jan 20, 2016 - Welcome to Math Studio Talk a video series that provides games, activities and models to help students..
Top 10 LaptopsMultimedia, Budget Multimedia, Gaming, Budget Gaming, Lightweight Gaming, Business, Budget Office, Workstation, Subnotebooks, Ultrabooks, Chromebooks Haferlach C, Grossmann V, Kohlmann A, Schindela S, Kern W, Schnittger S, Haferlach T. Deletion of the tumor-suppressor gene NF1 occurs in 5% of myeloid malignancies and is accompanied by a mutation in the remaining allele in half of the cases. Leukemia. 2012;26(4):834–9.Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR, et al. The landscape of cancer genes and mutational processes in breast cancer. Nature. 2012;486(7403):400–4.
Cawkwell L, Lewis FA, Quirke P. Frequency of allele loss of DCC, p53, RBI, WT1, NF1, NM23 and APC/MCC in colorectal cancer assayed by fluorescent multiplex polymerase chain reaction. Br J Cancer. 1994;70(5):813–8.Cooper DN, Upadhyaya M. The germline mutational spectrum in neurofibromatosis type 1 and genotype-phenotype correlations, Chapter 10. In: Upadhyaya M, Cooper DN, editors. Neurofibromatosis Type 1, vol. Chapter 10. Berlin: Springer Verlag; 2012. p. 115–34.Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–7.
It should be appreciated that the same gene can function in completely opposite ways in different cell types. In melanomas harbouring BRAF V600E mutations, a BRAF inhibitor induces remission of the tumour; however, the same drug is ineffective in colorectal cancer cells harbouring identical mutations. This has been attributed to the expression of EGFR which occurs in some colorectal cancers, but not in melanomas .Shima N, Alcaraz A, Liachko I, Buske TR, Andrews CA, Munroe RJ, Hartford SA, Tye BK, Schimenti JC. A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Nat Genet. 2007;39(1):93–8.Side L, Taylor B, Cayouette M, Conner E, Thompson P, Luce M, Shannon K. Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders. N Engl J Med. 1997;336(24):1713–20.
PCI-SIG, the standards committee behind PCI Express and related standards, has issued a warning about incompatibilities between their M.2 standard and Samsung's NGSFF/NF1 SSD form factor Kanchi KL, Johnson KJ, Lu C, McLellan MD, Leiserson MD, Wendl MC, Zhang Q, Koboldt DC, Xie M, Kandoth C, et al. Integrated analysis of germline and somatic variants in ovarian cancer. Nat Commun. 2014;5:3156.
Cancer Genome Atlas Research N. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315–22.Devarakonda S, Morgensztern D, Govindan R. Genomic alterations in lung adenocarcinoma. Lancet Oncol. 2015;16(7):e342–351.
Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, Shukla SA, Guo G, Brooks AN, Murray BA, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 2016;48(6):607–16.In an exploration of the somatic mutation landscape of 30 patients with syndromic (n = 8) or sporadic (n = 22) JMML, a combination of genome-wide DNA array analysis, whole-exome sequencing and targeted sequencing was used in paired germline and tumour samples . In total, 85 somatically acquired genetic alterations were found in 83% (25/30) of patients in this sub-cohort. Genes containing somatic variants detected by whole-exome sequencing, or previously reported to be mutated in JMML, were then sequenced in the full cohort of 118 JMML cases. A total of 122 secondary clonal abnormalities, in addition to initiating RAS pathway mutations, were identified in 49% (58/118) of patients . In addition, sequencing of isolated myeloid colonies demonstrated the coexistence of multiple RAS hits in the same myeloid progenitors in three of the JMML cases tested, challenging the concept of mutually exclusive RAS pathway mutations.Neuroblastoma is a neuroendocrine tumour that originates from neural crest cells of the sympathetic nervous system, with most tumours developing in the abdomen. Neuroblastoma is the second most common solid tumour in childhood and accounts for 8% of all childhood cancers. The treatment for neuroblastoma includes surgery, chemotherapy, radiation and bone marrow transplantation. Familial neuroblastoma cases comprise only a small fraction (~1–2%) of all neuroblastoma cases, and their genetic aetiology is relatively well understood [127, 128]. In contrast, far less is known of the genetic aetiology of sporadic neuroblastomas, despite their accounting for the majority of cases.The NF1 gene is spread over a large locus (350 kbp) at 17q11.2. It contains 61 exons, including four alternatively spliced exons, and is transcribed into a 12 kbp messenger RNA (mRNA) containing an open reading frame of 8454 nucleotides . Curiously, intron 27b, the largest intron of NF1 at 61 kbp, contains three embedded genes, OMGP, EVI2B and EVI2A, that are all transcribed in the opposite orientation to NF1 but whose protein products appear to have little or no interaction with neurofibromin .
As neurofibromin activity is a key to regulating the RAS/MAPK pathway, NF1 mutations are important in the acquisition of drug resistance, to BRAF, EGFR inhibitors, tamoxifen and retinoic acid in melanoma, lung and breast cancers and neuroblastoma. Other curiosities are observed, such as a high rate of somatic NF1 mutation in cutaneous melanoma, lung cancer, ovarian carcinoma and glioblastoma which are not usually associated with neurofibromatosis type 1. Somatic NF1 mutations may be critical drivers in multiple cancers. The mutational landscape of somatic NF1 mutations should provide novel insights into our understanding of the pathophysiology of cancer. The identification of high frequency of somatic NF1 mutations in sporadic tumours indicates that neurofibromin is likely to play a critical role in development, far beyond that evident in the tumour predisposition syndrome NF1.Walther MM, Herring J, Enquist E, Keiser HR, Linehan WM. von Recklinghausen’s disease and pheochromocytomas. J Urol. 1999;162(5):1582–6. K8NF-9 (Rev 1.x)主機板採用AMD平台，配備有許多最新設計，提供強大的表現功能，是消費者最佳 配備Serial ATA介面更能展現岀GA-K8NF-9 (Rev 1.x)在資料存取時的超高效能以及資料保護的特性.. The pathological significance of sporadic NF1 point mutations, especially putative missense mutations that have been identified in many sporadic tumours, is often unclear. Constitutional NF1 missense mutations represent about 15% of all NF1 mutations, but their frequency in sporadic tumours ranges widely from 15 to 71% [24, 25, 45, 72, 106, 143, 167, 170,171,172]. The characterization of such missense mutations has yielded new insights into the structure and function of neurofibromin. For example, through analysis of missense mutations, the arginine finger loop of the neurofibromin GRD has been found to be crucial for stabilizing the transition state of the GTPase reaction, and many missense mutations in the GRD have been found to exert a significant, pathological effect on Ras activity levels [36, 173, 174].
Markedly reduced NF1 mRNA expression in ADC has been found to confer both an intrinsic and an acquired resistance to EGFR inhibitors . By performing a genome-wide siRNA screen of both a human lung cancer cell line and a murine mutant EGFR-driven lung ADC, this revealed reduced NF1 mRNA expression in both, and furthermore, whilst the EGFR inhibitor erlotinib failed to fully inhibit RAS-ERK signalling when neurofibromin levels were reduced, treatment of neurofibromin-deficient lung cancers with MEK inhibitor restored sensitivity to erlotinib .Welander J, Soderkvist P, Gimm O. The NF1 gene: a frequent mutational target in sporadic pheochromocytomas and beyond. Endocr Relat Cancer. 2013;20(4):C13–17.Neurofibromin 1 (NF1) is a gene in humans that is located on chromosome 17. NF1 codes for neurofibromin, a GTPase-activating protein that negatively regulates RAS/MAPK pathway activity by accelerating the hydrolysis of Ras-bound GTP. NF1 has a high mutation rate and mutations in NF1 can alter cellular growth control, and neural development, resulting in neurofibromatosis type 1 (NF1, also known as von Recklinghausen syndrome). Symptoms of NF1 include disfiguring cutaneous neurofibromas (CNF), café au lait pigment spots, plexiform neurofibromas (PN), skeletal defects, optic nerve gliomas, life-threatening malignant peripheral nerve sheath tumors (MPNST), attention deficits, learning deficits and other cognitive disabilities. Despite all the cancer genome information available regarding NF1, it remains unclear why NF1 patients are predisposed only to certain types of tumours. Why, for example, are NF1 patients not predisposed to lung tumours given that at least 10% of all sporadic lung cancers have NF1 mutations [8, 65, 72, 166]? GA-K8NF-9. (rev
The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many types of cells, including nerve cells and specialized cells called oligodendrocytes and.. It has been suggested that the quantitative differences in expression between the different isoforms may be related to the phenotypic variability of neurofibromatosis type 1 patients. Bashashati A, Ha G, Tone A, Ding J, Prentice LM, Roth A, Rosner J, Shumansky K, Kalloger S, Senz J, et al. Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling. J Pathol. 2013;231(1):21–34.The capacity of NF1 mutations to act both cooperatively and exclusively without BRAF and NRAS mutations in melanoma may be mediated through pathways other than the MAPK pathway. Maertens and colleagues have identified increased activation of the PI3K/AKT/mTOR pathway in BRAF/NF1 double mutants, and a combinatorial MEK marker and mTOR inhibitor treatment has proven effective in many MEK inhibitor-resistant neoplasms . In a glioblastoma animal model, NF1 cooperates with both TP53 and PTEN, but no co-occurrence of NF1 and BRAF mutations is seen . Moreover, whilst simultaneous inactivation of Nf1 and expression of K-RasG12D in mouse haematopoietic cells results in AML that was fatal in primary mice within 4 weeks, in ovarian serous carcinomas, cooperation between mutant TP53 and NF1 results in a poor prognosis [92, 117]. In addition, an association between inactivated NF1 and ZNF423 levels in neuroblastomas has been identified as a putative prognostic marker .Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR. A census of human cancer genes. Nat Rev Cancer. 2004;4(3):177–83.Matsui I, Tanimura M, Kobayashi N, Sawada T, Nagahara N, Akatsuka J. Neurofibromatosis type 1 and childhood cancer. Cancer. 1993;72(9):2746–54.