AppId is over the quota
Researchers studying a rare, lethal childhood tumor of the brainstem discovered that nearly 80 percent of the tumors have mutations in genes not previously tied to cancer. Early evidence suggests the alterations play a unique role in other aggressive pediatric brain tumors as well.
The findings from the St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project (PCGP) offer important insight into a poorly understood tumor that kills more than 90 percent of patients within two years. The tumor, diffuse intrinsic pontine glioma (DIPG), is found almost exclusively in children and accounts for 10 to 15 percent of pediatric tumors of the brain and central nervous system.
"We are hopeful that identifying these mutations will lead us to new selective therapeutic targets, which are particularly important since this tumor cannot be treated surgically and still lacks effective therapies," said Suzanne Baker, Ph.D., co-leader of the St. Jude Neurobiology and Brain Tumor Program and a member of the St. Jude Department of Developmental Neurobiology. She is a corresponding author of the study published in the January 29 online edition of the scientific journal Nature Genetics.
DIPG is an extremely invasive tumor that occurs in the brainstem, which is at the base of the skull and controls such vital functions as breathing and heart rate. DIPG cannot be cured by surgery and is accurately diagnosed by non-invasive imaging. As a result, DIPG is rarely biopsied in the U.S. and little is known about it.
Cancer occurs when normal gene activity is disrupted, allowing for the unchecked cell growth and spread that makes cancer so lethal. In this study, investigators found 78 percent of the DIPG tumors had alterations in one of two genes that carry instructions for making proteins that play similar roles in packaging DNA inside cells. Both belong to the histone H3 family of proteins. DNA must be wrapped around histones so that it is compact enough to fit into the nucleus. The packaging of DNA by histones influences which genes are switched on or off, as well as the repair of mutations in DNA and the stability of DNA. Disruption of any of these processes can contribute to cancer.
Researchers said that the mutations seem unique to aggressive childhood brain tumors.
"It is amazing to see that this particular tumor type appears to be characterized by a molecular 'smoking gun' and that these mutations are unique to fast-growing pediatric cancers in the brain," said Richard K. Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis and one of the study's corresponding authors. "This is exactly the type of result one hopes to find when studying the genomes of cancer patients."
The results are the latest from the PCGP, an ambitious three-year effort to sequence the complete normal and cancer genomes of 600 children with some of the most poorly understood and aggressive pediatric cancers. The human genome includes the complete set of instructions needed to assemble and sustain human life. The goal is to identify differences that explain why cancer develops, spreads and kills. Researchers believe the findings will provide the foundation for new tools to diagnose, treat or prevent the disease.
For this study, researchers sequenced the complete normal and cancer genomes of seven patients with DIPG. "The mutations were found at such high frequency in the cancer genomes of those seven patients that we immediately checked for the same alterations in a larger group of DIPGs," Baker said. When researchers sequenced all 16 of the related genes that make closely related variants of histone H3 proteins in an additional 43 DIPGs, they found many of the tumors contained the same mistakes in only two of these genes.
Of the 50 DIPG tumors included in this study, 60 percent had a single alteration in the makeup of the H3F3A gene. When the mutated gene was translated into a protein, the point mutation led to the substitution of methionine for lysine as the 27th amino acid in this variant of histone H3 protein. Another 18 percent of the DIPG patients carried the same mistake in a different gene, HIST1H3B.
Researchers are now working to understand how mutations in H3F3A and HIST1H3B impact cell function and contribute to cancer. Earlier research provides some clues. The lysine that is mutated is normally targeted by enzymes that attach other molecules to histone H3, influencing how it interacts with other proteins that regulate gene expression, Baker said. Mutations in the enzymes that target histone H3 have been identified in other cancers, but this is the first report showing a specific alteration of histones in cancer.
H3F3A and HIST1H3B were also mutated in other aggressive childhood brain tumors, glioblastoma, that develop outside the brain stem. Of 36 such tumors included in this study, 36 percent carried one of three distinct point mutations in the genes. The alterations included another single change in the makeup of H3F3A not found in DIPGs.
The histone H3 genes, however, were not mutated in any of the 252 other childhood tumors researchers checked for this study. The list included the brain tumors known as low-grade gliomas, medulloblastomas and ependymomas plus other cancers outside the brain and nervous system. The H3 changes have not been reported in any other cancers, including adult glioblastoma. "This suggests these particular mutations give a very important selective advantage, particularly in the developing brainstem and to a lesser degree in the developing brain, which leads to a terribly aggressive brain tumor in children, but not in adults," Baker said.
"This discovery would not have been possible without the unbiased approach taken by the Pediatric Cancer Genome Project," Baker said. "The mutations had not been reported in any other tumor, so we would not have searched for them in DIPGs. Yet the alterations clearly play an important role in generating this particular tumor."
Additional References Citations Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. The study's first authors are Gang Wu, Alberto Broniscer and Troy McEachron, all of St. Jude. The study's other corresponding authors are Jinghui Zhang and James Downing, both of St. Jude. The other study authors are Charles Lu, Li Ding and Elaine Mardis, all of Washington University; and Barbara Paugh, Jared Becksfort, Chunxu Qu, Robert Huether, Matthew Parker, Junyuan Zhang, Amar Gajjar, Michael Dyer, Charles Mullighan, Richard Gilbertson and David Ellison, all of St. Jude.
The research was funded in part by the PCGP, including Kay Jewelers, a lead project sponsor; the National Institutes of Health, the Sydney Schlobohm Chair of Research from the National Brain Tumor Society; the Cure Starts Now Foundation, Smile for Sophie Forever Foundation, Tyler's Treehouse Foundation, Musicians Against Childhood Cancer, the Noyes Brain Tumor Foundation and ALSAC.
St. Jude Children's Research Hospital Please use one of the following formats to cite this article in your essay, paper or report:
MLA
St. Jude Children's Research Hospital. "Mutations Tied To Aggressive Childhood Brain Tumors Revealed By Cancer Sequencing Initiative." Medical News Today. MediLexicon, Intl., 30 Jan. 2012. Web.
5 Feb. 2012.
St. Jude Children's Research Hospital. (2012, January 30). "Mutations Tied To Aggressive Childhood Brain Tumors Revealed By Cancer Sequencing Initiative." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/240924.php.
Please note: If no author information is provided, the source is cited instead.
Rate this article:
(Hover over the stars then click to rate) Patient / Public:
or Health Professional:
Add Your Opinion
Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.
If you write about specific medications or operations, please do not name health care professionals by name.
All opinions are moderated before being included (to stop spam)
Your Name:* E-mail Address:* Title For Opinion:* Opinion:* This is to help prevent SPAM submissions. Please enter the words exactly as they appear, including capital letters and punctuation.** Fields marked with a * need to be filled in before you hit the submit button.
Contact Our News Editors
For any corrections of factual information, or to contact the editors please use our feedback form.
Please send any medical news or health news press releases to:
back to top
home
popular news by year
all written articles
health videos
contact us
your news:
news category list
personalize homepage
weekly newsletters
daily news alerts
company:
about us
advertising
news licensing
article submission
more:
accessibility
help / faq
links
free website feeds
free tools & content
Privacy Policy | Terms and ConditionsMediLexicon International Ltd
Bexhill-on-Sea, United Kingdom
MediLexicon International Ltd © 2004-2012 All rights reserved.
Cancer / OncologyWhat is Cancer?
Cancer is a class of diseases characterized by out-of-control cell growth. There are over 100 different types of cancer, and each is classified by the type of cell that is initially affected. Read more...Most Popular Articles 1 Month 3 Months 6 Months 1US Cancer Screening Below National Targets2Tumors Continue Growing Even When Cells Get Old3Breast Cancer Survival - Why Avastin And Sutent Don't Help4Cancer Deaths - Enormous Drop Over Last 20 Years, USA5Cancer Screening Rates Low Among Ethnic Groups, USA6Malignant Melanoma Recurrence - How To Avoid It After Targeted Treatment77% Of Americans Have Oral HPV8Statins May Work Against Certain Breast Cancers 1US Cancer Screening Below National Targets2Tumors Continue Growing Even When Cells Get Old3Roche's Avastin Receives EU Approval For Ovarian Cancer4Breast Cancer Survival - Why Avastin And Sutent Don't Help5Cancer Deaths - Enormous Drop Over Last 20 Years, USA6Cancer Screening Rates Low Among Ethnic Groups, USA7Coffee Emerges As Protective Against Cancer And Other Diseases8Breast Cancer Survival In Younger Breast Cancer Patients Improves With Bone Drug9Malignant Melanoma Recurrence - How To Avoid It After Targeted Treatment10Cancer Vaccine Significantly Reduces Tumor Size 1US Cancer Screening Below National Targets2Tumors Continue Growing Even When Cells Get Old3Roche's Avastin Receives EU Approval For Ovarian Cancer4Breast Cancer Survival - Why Avastin And Sutent Don't Help5Cancer Deaths - Enormous Drop Over Last 20 Years, USA6Cancer Screening Rates Low Among Ethnic Groups, USA7Coffee Emerges As Protective Against Cancer And Other Diseases8Breast Cancer Survival In Younger Breast Cancer Patients Improves With Bone Drug9Malignant Melanoma Recurrence - How To Avoid It After Targeted Treatment10Cancer Vaccine Significantly Reduces Tumor Size Follow Our Cancer News On Twitter
Get the latest news for this category delivered straight to your Twitter account. Simply visit our Cancer / Oncology Twitter account and select the 'follow' option.Conditions Information-- select from list --Abscess (Dental)AchalasiaAchilles TendinitisAcid RefluxAcneAcoustic Neuroma (Vestibular Schwannoma)AcromegalyActinomicosisAcute Lymphoblastic LeukemiaAcute Myeloid LeukemiaAddictionAddison’s Disease (Primary Adrenal Insufficiency)ADHDAgoraphobiaAir Embolism (Gas Embolism)Alcohol PoisoningAlcoholic Liver DiseaseAlcoholismAlopecia AreataAltitude Sickness (Acute Mountain Sickness)Alzheimer's DiseaseAMD / Macular DegenerationAmenorrheaAmnesiaAmniocentesisAnagen EffluviumAnal CancerAnal FissureAnal Itching (Itchy Bottom)AnaphylaxisAndrogen Insensitivity Syndrome (AIS)AnemiaAnemia (Vitamin Deficiency)AneurysmAngerAnginaAngioedemaAnorexia & BulimiaAntiphospholipid Syndrome (Hughes Syndrome)AnxietyAphasiaAppendicitisArrhythmiaArthritisAsperger SyndromeAsthmaAstigmatismAtaxiaAtrial FibrillationAtrophic Vaginitis (Vaginal Atrophy)AutismAvian InfluenzaBack PainBacterial VaginosisBaker's Cyst (Popliteal Cyst)BalanitisBartholin's CystBed Sores (Pressure Ulcers)Bell's PalsyBinge Eating DisorderBipolar DisorderBird FluBladder cancerBladder StonesBlepharitisBody Dysmorphic DisorderBody Odor (B.O.)Boils, furuncles, carbunclesBone CancerBorderline Personality Disorder (BPD)BotulismBrain Abscess (Cerebral Abscess)Breast CancerBreast Cancer (Male)Breast LumpsBronchiectasis (Bronchiectasia)BronchitisBursitisCancerCandidiasisCarbon Monoxide PoisoningCarpal Tunnel SyndromeCartilage DamageCataractsCatatonic SchizophreniaCelluliteCellulitisCerebral PalsyCerebrovascular DiseaseCervical SpondylosisCharcot-Marie-Tooth DiseaseChickenpoxChildhood SchizophreniaChlamydiaCholecystitis (Gallbladder Inflammation)CholeraCholestasis Of Pregnancy (Obstetric Cholestasis)CholesterolChronic Fatigue Syndrome (CFS)Chronic Fatigue Syndrome (CFS)Chronic Kidney FailureChronic Rhinosinusitis (CRS)CirrhosisCJDClaustrophobiaClostridium Difficile (C. Difficile)Clubfoot (Talipes Equinovarus)Cluster HeadacheCold SoresColicColon CancerColorectal CancerComa (Comatose)Common ColdComplex Regional Pain Syndrome (CRPS)ConcussionCongenital Heart Disease (Congenital Heart Defect)Conjunctivitis (allergic)Conjunctivitis (infective)ConstipationCOPD & EmphysemaCorns / CallusesCoronary Heart Disease (Coronary Artery Disease)Costello SyndromeCoughCrabs (Pubic Lice)CraniosynostosisCreutzfeldt-Jakob disease (CJD)CristoporidiosisCrohn's DiseaseCroupCryptorchidism (Undescended Testicle)Cushing's SyndromeCystic FibrosisCystitisCystsCytomegalovirus (CMV)DandruffDeep Vein ThrombosisDehydrationDementiaDengue Fever?DepressionDetached RetinaDHTDiabetesDiabetes InsipidusDiabetic RetinopathyDiarrheaDiphtheriaDiscoid Eczema (Nummular Dermatitis)Disorganized Schizophrenia (Hebephrenia)DiverticulitisDouble Vision (Diplopia)Down SyndromeDry Eye SyndromeDry Mouth (Xerostomia)Dupuytren’s ContractureDysenteryDyslexiaDysphagiaDyspraxiaDystoniaE.coliEctopic PregnancyEctropionEczemaEdemaEmbolismEmphysemaEncephalitisEndocarditisEndometriosisEnuresis - BedwettingEpidermolysis BullosaEpiglottitisEpilepsyEpiphora (Watering Eye)Erectile DysfunctionEsophageal CancerEsophagitisEuthanasia (Assisted Suicide)Exophthalmos (Bulging Eyes)Eye Melanoma (Ocular Melanoma)Febrile Seizures (Convulsions)FeverFibroidsFibromyalgiaFlat Feet (Fallen Arches)FlatulenceFood AllergyFracture (Broken Bones)FrostbiteFrozen ShoulderGallstonesGanglion CystGangreneGastroenteritis / Food PoisoningGenital WartsGERDGiardiasisGilbert SyndromeGlandular FeverGlaucomaGlomerulonephritisGlue EarGluten Intolerance / Celiac DiseaseGoiter (Goitre)GonorrheaGoutGraves’ DiseaseGuillain-Barré SyndromeGum Disease (Gingivitis)Hair Loss / BaldnessHalitosis (Bad Breath)HangoverHay FeverHead LiceHeadachesHeart AttackHeart Block (AV Bundle/Bundle Branch Block)Heart DiseaseHeart FailureHeartburnHeat Rash (Prickly Heat)Heel PainHemochromatosisHemophiliaHemroids / HemorrhoidsHepatitisHerniaHerpesHiccupsHiccups (Hiccoughs)High Blood PressureHirsutism (Excessive Hairiness)HIV / AIDSHivesHormone Replacement Therapy (HRT)Huntington's DiseaseHydrocephalus (Water On The Brain)Hyperhidrosis (Excessive Sweating)HypertensionHyperthyroidismHypertrophic CardiomyopathyHypertrophic CardiomyopathyHypochondriaHypoglycemiaHypotensionHypothermiaHypothyroidismHysterectomyImpacted Wisdom TeethImpetigoIncontinence (bowel)Incontinence (urinary)IndigestionInfant JaundiceInfertilityInfluenza / FluIngrown ToenailInsomniaIrregular Periods (Oligomenorrhea)Irritable Bowel Syndrome (IBS)Irritable Hip (Acute Transient Synovitis)Japanese EncephalitisJaundice (icterus)Jet LagKawasaki DiseaseKetosisKidney CancerKidney Infection (Pyelonephritis)Kidney StonesLactose IntoleranceLaryngeal Cancer (Cancer Of The Larynx)LaryngitisLazy EyeLeg CrampsLegionnaires' DiseaseLeukemiaLichen PlanusListeria Infection (Listeriosis)Liver CancerLung CancerLupusLyme DiseaseLymphedemaLymphomaMal De Debarquement Syndrome (MdDS)MalariaMalnutritionMarfan SyndromeMastitisMeaslesMeniere's diseaseMeningitisMenopauseMental HealthMesotheliomaMetatarsalgia (Stone Bruise)MigraineMolesMolluscum ContagiosumMorning Sickness (Nausea Gravidarum)Morton's NeuromaMotion Sickness (Travel Sickness)Motor Neuron DiseaseMouth CancerMRSAMultiple MyelomaMultiple SclerosisMumpsMunchausen SyndromeMunchausen Syndrome By ProxyMuscular Dystrophy (MD)Myasthenia Gravis (Goldflam Disease)Nail Fungal InfectionNarcissistic Personality DisorderNarcolepsyNasal PolypsNDM-1Necrotizing FasciitisNeurofibromatosisNeuromyelitis Optica (Devic's Disease)NeuropathyNicotine Dependence (Dangers Of Smoking)Noonan SyndromeNorovirus InfectionObesityObsessive Compulsive DisorderObsessive Compulsive Disorder (OCD)Obstructive Sleep Apnea (OSA)Occupational AsthmaOpioid-Induced Constipation (OIC)Oral Thrush (Babies)Oral Thrush (Oral Candidiasis)OsteoarthritisOsteochondritis DissecansOsteomyelitis (Bone Infection)OsteopathyOsteoporosisOtitis Externa (Swimmer's Ear)Ovarian CancerOvarian CystPaget's Disease (Of Bone)PainPainful Intercourse (Dyspareunia)Pancreatic CancerPancreatitis (acute)Pancreatitis (chronic)Panic AttacksParanoid SchizophreniaParasitesParkinson's DiseasePelvic Inflammatory DiseasePeptic UlcersPericarditisPeriod PainsPeripheral Artery Disease (PAD)Personality DisordersPilesPimplesPinworms (Threadworms)PleurisyPneumococcal DiseasePneumoniaPolioPost Traumatic Stress Disorder (PTSD)Postherpetic NeuralgiaPostpartum DepressionPrader-Willi SyndromePremature EjaculationPrimary Sclerosing CholangitisProgeriaProstate CancerPsoriasisPsoriasisPulmonary Edema (Oedema)Pulmonary EmbolismQ FeverRabiesRadiation Sickness (Radiation Poisoning)Ramsay Hunt SyndromeRaynaud's DiseaseRectocele (Proctocele)Repetitive Strain Injury (RSI)Restless Legs SyndromeRheumatic FeverRheumatoid ArthritisRhinitis, Non-AllergicRicketsRingwormRosaceaRubellaRuptured SpleenSalivary Gland CancerSalmonellaSARSScabiesScarlet Fever (Scarlatina)Schistosomiasis (Bilharzia)Schizoaffective DisorderSchizophreniaSciaticaSclerodermaScoliosisScurvySeasonal Affective DisorderSexual Addiction (Nymphomania)ShinglesShort Stature (Dwarfism)SinusitisSjogren's SyndromeSkin Cancer / MelanomaSlapped Cheek SyndromeSocial Anxiety DisorderSpina BifidaSpinal Muscular AtrophySquint (Strabismus)StammeringStrep Throat / Sore ThroatStressStress IncontinenceStrokeStye (Hordeolum)Subarachnoid HemorrhageSuicidal ThoughtsSwine FluSyphilisTachycardia (Fast Heart Beat)Tapeworms (Cestodes)Teeth Grinding (Bruxism)Tendinitis (Tendonitis)Testicular CancerTesticular TorsionTetanusThyroid CancerThyroid NodulesTinnitusTiredness / FatigueTobacco Smoke ToxinsTonsillitisTourette SyndromeToxic Shock Syndrome (TSS)Transient Ischemic Attacktransient ischemic attackTraumatic Brain Injury (TBI)Trigeminal NeuralgiaTriple X SyndromeTuberculosisTurner SyndromeTyphoidUlcerative ColitisUmbilical HerniaUrinary Tract Infection (UTI)UveitisVaculitis (Angiitis)Vaginal CancerVaginismusVaginitisValley Fever (Coccidioidomycosis)VaricoceleVaricose Eczema (Stasis Dermatitis)Varicose VeinsVentricular FibrillationVertigoVesicoureteral Reflux (VUR)Vitamin B12 DeficiencyVocal Cord Paresis (Paralysis)Von Willebrand DiseaseVulvar Cancer (Vulval Cancer)VulvodyniaWartsWater On The Knee (Knee Effusion)Water Retention (Fluid Retention)Wegener's GranulomatosisWernicke-Korsakoff SyndromeWest Nile Virus (WNV)Wheat AllergyWhipple's DiseaseWilliams SyndromeWilms’ Tumor (Nephroblastoma)Wolff-Parkinson-White SyndromeYellow FeverYipsZollinger-Ellison Syndrome
View list of all 'What Is...' articles »
Posts
0 comments: on "Mutations Tied To Aggressive Childhood Brain Tumors Revealed By Cancer Sequencing Initiative"
Post a Comment