Distinct patterns of 1p and 19q alterations identify subtypes of human gliomas that have different prognoses |
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Authors: | Artemis P Vogazianou Raymond Chan L Magnus B?cklund Danita M Pearson Lu Liu Cordelia F Langford Simon G Gregory V Peter Collins Koichi Ichimura |
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Institution: | Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke''s Hospital, Cambridge (A.P.V., R.C., D.M.P., L.L., V.P.C., K.I.); Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (L.M.B.); The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge (C.F.L., S.G.G.); Duke Center for Human Genetics, Duke University Medical Center, Durham, North Carolina (S.G.G.) |
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Abstract: | We studied the status of chromosomes 1 and 19 in 363 astrocytic and oligodendroglial tumors. Whereas the predominant pattern of copy number abnormality was a concurrent loss of the entire 1p and 19q regions (total 1p/19q loss) among oligodendroglial tumors and partial deletions of 1p and/or 19q in astrocytic tumors, a subset of apparently astrocytic tumors also had total 1p/19q loss. The presence of total 1p/19q loss was associated with longer survival of patients with all types of adult gliomas independent of age and diagnosis (P = .041). The most commonly deleted region on 19q in astrocytic tumors spans 885 kb in 19q13.33–q13.41, which is telomeric to the previously proposed region. Novel regions of homozygous deletion, including a part of DPYD (1p21.3) or the KLK cluster (19q13.33), were observed in anaplastic oligodendrogliomas. Amplifications encompassing AKT2 (19q13.2) or CCNE1 (19q12) were identified in some glioblastomas. Deletion mapping of the centromeric regions of 1p and 19q in the tumors that had total 1p/19q loss, indicating that the breakpoints lie centromeric to NOTCH2 within the pericentromeric regions of 1p and 19q. Thus, we show that the copy number abnormalities of 1p and 19q in human gliomas are complex and have distinct patterns that are prognostically predictive independent of age and pathological diagnosis. An accurate identification of total 1p/19q loss and discriminating this from other 1p/19q changes is, however, critical when the 1p/19q copy number status is used to stratify patients in clinical trials. |
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Keywords: | array-CGH astrocytoma centromere deletion microarray oligodendroglioma translocation |
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