title: CDKN2A loss is associated with shortened overall survival in lower-grade (World Health Organization Grades II-III) astrocytomas.
abstract: Lower-grade (World Health Organization Grades II and III) gliomas vary widely in clinical behavior and are classified as astrocytic, oligodendroglial, or mixed. Anaplasia depends greatly on mitotic activity, with CDKN2A loss considered as the most common mechanism for cell cycle dysregulation. We investigated whether loss of the CDKN2A gene is associated with overall survival across pathologically and genetically defined glioma subtypes. After adjustment for IDH mutation, sex, and age, CDKN2A deletion was strongly associated with poorer overall survival in astrocytomas but not in oligodendrogliomas or oligoastrocytomas. Molecular classification of astrocytomas by IDH mutation, TP53 mutation, and /or ATRX loss of expression revealed that CDKN2A loss in IDH/TP53 mutated tumors was strongly associated with worse overall survival. CDKN2A loss in IDH mutated tumors with ATRX loss was only weakly associated with worse overall survival. These findings suggest that CDKN2A testing may provide further clinical aid in lower-grade glioma substratification beyond IDH mutation and 1p19q codeletion status, particularly in IDH/TP53 mutated astrocytomas.
authors: From the Departments of Neurology, Pediatrics, and Neurosurgery, Stanford University School of Medicine, Stanford (HV); Department of Anatomic Pathology, University of California San Francisco Medical School (GFR, MP, AP); Division of Neuroepidemiology (HMH, TR, JKW, MRW, KMW), Departments of Neurological Surgery (REM, AMM, JJP, AP) and Epidemiology and Biostatistics (AMM); and Institute for Human Genetics, University of California San Francisco (JKW, MRW, KMW), San Francisco, California.
authors: Gerald F
authors: GF
authors: Reis
authors: Melike
authors: M
authors: Pekmezci
authors: Helen M
authors: HM
authors: Hansen
authors: Terri
authors: T
authors: Rice
authors: Roxanne E
authors: RE
authors: Marshall
authors: Annette M
authors: AM
authors: Molinaro
authors: Joanna J
authors: JJ
authors: Phillips
authors: Hannes
authors: H
authors: Vogel
authors: John K
authors: JK
authors: Wiencke
authors: Margaret R
authors: MR
authors: Wrensch
authors: Kyle M
authors: KM
authors: Walsh
authors: Arie
authors: A
authors: Perry
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000378:metabolism* / Q000401:mortality*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D007521:Isocitrate Dehydrogenase