title: Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors.
abstract: OBJECTIVE
  The histological diagnosis of human gliomas is of great importance for estimating patient prognosis and guiding therapy but suffers from being subjective and, therefore, variable. We hypothesized that molecular genetic analysis could provide a more objective means to classify tumors and, thus, reduce diagnostic variability.
  
  
  METHODS
  We performed molecular genetic analysis on 91 nonselected gliomas for 1p, 19q, 10q, TP53, epidermal growth factor receptor, and cyclin-dependent kinase 4 abnormalities and compared with the consensus diagnoses established among four independent neuropathologists.
  
  
  RESULTS
  There were six astrocytomas, seven anaplastic astrocytomas, 45 glioblastomas, 21 oligodendrogliomas, eight anaplastic oligodendrogliomas, three oligoastrocytomas, and one anaplastic oligoastrocytoma. Twenty-nine cases had either 1p or 19qloss of heterozygosity (LOH) while retaining both copies of 10q, of which 25 (86%) were histologically oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, or anaplastic oligoastrocytoma. As for the oligodendroglial tumors, unanimous agreement of the initial diagnoses was almost restricted to those cases with combined 1p/19qLOH, whereas all nine tumors without 1p loss initially received variable diagnoses. Interestingly, TP53 mutation was inversely related to 1pLOH in all gliomas (P = 0.0003) but not 19qLOH (P = 0.15).
  
  
  CONCLUSIONS
  These data demonstrate that molecular genetic analysis of 1p/19q/10q/TP53 has significant diagnostic value, especially in detecting oligodendroglial tumors. In addition, 1pLOH and TP53 mutations in gliomas may be markers of oligodendroglial and astrocytic pathways, respectively, which may separate gliomas with the same histological diagnosis, especially oligodendroglial tumors and glioblastomas. Testing for those molecular genetic alterations would be essential to obtain more homogeneous sets of gliomas for the future clinical studies.
authors.affiliation: Department of Neurosurgery, University of Tokyo Hospital, Tokyo 113-8655, Japan. kueki-tky@umin.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ueki
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Takanori
authors.initials: T
authors.lastname: Hirose
authors.forename: Junko
authors.initials: J
authors.lastname: Hirato
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Funada
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Fujimaki
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hojo
authors.forename: Osami
authors.initials: O
authors.lastname: Kubo
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ide
authors.forename: Masaaki
authors.initials: M
authors.lastname: Usui
authors.forename: Chikayuki
authors.initials: C
authors.lastname: Ochiai
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Akitake
authors.initials: A
authors.lastname: Mukasa
authors.forename: Akio
authors.initials: A
authors.lastname: Asai
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kirino
mesh_terms: D000483:Alleles; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008967:Molecular Biology; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D009837:Oligodendroglioma / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases