Genetic differences between neurocytoma and dysembryoplastic neuroepithelial tumor and oligodendroglial tumors.
OBJECTIVE
Because of their histological similarities, it is occasionally difficult to differentiate neurocytoma and dysembryoplastic neuroepithelial tumor (DNT) from oligodendroglial tumors. This study was conducted to investigate genetic differences among these tumor types in terms of loss of heterozygosity on chromosomes 1p and 19q, and p53 gene mutation.


METHODS
A total of 24 tumors were analyzed, consisting of eight central neurocytomas, three DNTs, seven oligodendrogliomas, four oligoastrocytomas, and two undetermined extraventricular tumors with neurocytoma features (ETNFs). Allelic loss was determined using microsatellite markers that cover the common deletions on chromosomes 1p and 19q in oligodendrogliomas. A p53 gene mutation was identified using polymerase chain reaction-single-strand conformation polymorphism analysis and subsequent direct sequencing. Immunohistochemical studies with synaptophysin and electron microscopy investigations were also conducted. Allelic loss on 1p and 19q was detected in six oligodendrogliomas (86%) and in three oligoastrocytomas (75%), but in none of the central neurocytomas or DNTs. A p53 missense mutation was detected at codon 161 (GCC-->ACC, Ala-->Thr) in only one oligoastrocytoma without allelic loss. Synaptophysin was expressed in all central neurocytomas and DNTs, in three oligodendrogliomas (43%), and in three oligoastrocytomas (75%). Of the ETNFs, one demonstrated synaptophysin expression and neural ultrastructures but lacked genetic alterations, whereas the other showed allelic loss on 1p and 19q but was negative immunohistochemically and ultrastructurally. The former was diagnosed as a potential intraparenchymal neurocytoma and the latter as an oligodendroglioma.


CONCLUSIONS
Despite histological similarities, central neurocytomas and DNTs are genetically distinct from oligodendroglial tumors. Examination for allelic loss on 1p and 19q and for p53 mutation can be useful for making this distinction.
Fujisawa
Hironori
H
Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. fujisawa@ns.m.kanazawa-u.ac.jp
Marukawa
Kohei
K
Hasegawa
Mitsuhiro
M
Tohma
Yasuo
Y
Hayashi
Yutaka
Y
Uchiyama
Naoyuki
N
Tachibana
Osamu
O
Yamashita
Junkoh
J
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D018699:Coated Vesicles / Q000648:ultrastructure; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009154:Mutation; D018302:Neoplasms, Neuroepithelial / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology; D018306:Neurocytoma / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D009837:Oligodendroglioma / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D016708:Synaptophysin / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016708:Synaptophysin; D016159:Tumor Suppressor Protein p53