Clonality of oligoastrocytomas.
Oligoastrocytomas (OA) are mixed glial tumors that show morphologic features of both oligodendrogliomas and astrocytomas. The histogenesis of these tumors remains undefined. The aim of this study was to investigate the clonality of OA on the basis of tumor-dependent genetic alterations and tumor-independent X-chromosome inactivation. We microdissected 11 biphasic OA and subjected the oligodendroglial and astrocytic components to allelic loss analysis of chromosomes 1p, 9p21, 10q, 13q, 17p, and 19q; TP53 immunohistochemical and mutation analyses; and X-linked HUMARA gene methylation study. On the basis of the genetic findings, we categorized these tumors into 3 groups. Group 1 consisted of 4 tumors that showed identical genetic aberrations in the 2 histologic elements, characterized by allelic loss on 1p and 19q. These results suggest that group 1 tumors are of monoclonal origin and share a precursor cell with oligodendrogliomas. Group 2 consisted of 5 tumors characterized by losses on 1p and 19q, with additional allelic losses on chromosomes 9p, 10q, 13q and/or 17p. Four of these tumors were of the anaplastic type. Thus, group 2 tumors may be regarded as advanced variants of group 1 OA with heterogeneous genetic changes during clonal expansion. The X-chromosome inactivation analysis confirmed the monoclonality of groups 1 and 2 OA. Group 3 consisted of two tumors that showed divergent allelic loss patterns in the 2 histologic components. Mutation and overexpression of TP53 were detectable in the astrocytic components only. These findings raise the possibility that group 3 tumors have a biclonal origin. In conclusion, our results suggest that OA are predominantly of monoclonal origin but that a small subset of tumors may be derived from different precursors.
Dong
Zhi-Qian
ZQ
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, China.
Pang
Jesse Chung-Sean
JC
Tong
Carol Yuen-Kwan
CY
Zhou
Liang-Fu
LF
Ng
Ho-Keung
HK
D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D002999:Clone Cells; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004210:Dissection; D004303:Dosage Compensation, Genetic; D005260:Female; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008745:Methylation; D008846:Micromanipulation; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C410798:AR protein, human; D004273:DNA, Neoplasm; D005819:Genetic Markers; D011944:Receptors, Androgen; D016159:Tumor Suppressor Protein p53