A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma

被引:531
作者
Jenkins, Robert B.
Blair, Hilary
Ballman, Karla V.
Giannini, Caterina
Arusell, Robert M.
Law, Mark
Flynn, Heather
Passe, Sandra
Felten, Sara
Brown, Paul D.
Shaw, Edward G.
Buckner, Jan C.
机构
[1] Mayo Clin, Rochester, MN USA
[2] Merit Care Community Clin Oncol Program, Fargo, ND USA
[3] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA
关键词
D O I
10.1158/0008-5472.CAN-06-1796
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Combined deletion of chromosomes 1p and 19q is associated with improved prognosis and responsiveness to therapy in patients with anaplastic oligodendroglioma. The deletions usually involve whole chromosome arms, suggesting a t(1;19)(q10;p10). Using stem cell medium, we cultured a few tumors. Paraffin-embedded tissue was obtained from 21 Mayo Clinic patients and 98 patients enrolled in 2 North Central Cancer Treatment Group (NCCTG) low-grade glioma trials. Interphase fusion of CEP1 and 19p12 probes detected the t(1;19). 1p/19q deletions were evaluated by fluorescence in situ hybridization. Upon culture, one oligodendroglioma contained an unbalanced 45,XX,t(1;19)(q10;p10). CEP1/19p12 fusion was observed in all metaphases and 74% of interphase nuclei. Among Mayo Clinic oligodendrogliomas, the prevalence of fusion was 81%. Among NCCTG patients, CEP1/19p12 fusion prevalence was 55%, 47%, and 0% among the oligodendrogliomas, mixed oligoastrocytomas, and astrocytomas, respectively. Ninety-one percent of NCCTG gliomas with 1p/19q deletion and 12% without 1p/19q deletion had CEP1/19p12 fusion (P < 0.001, chi(2) test). The median overall survival (OS) for all patients was 8.1 years without fusion and 11.9 years with fusion (P = 0.003). The median OS for patients with low-grade oligodendroglioma was 9.1 years without fusion and 13.0 years with fusion (P = 0.01). Similar significant median OS differences were observed for patients with combined 1p/19q deletions. The absence of alterations was associated with a significantly shorter OS for patients who received higher doses of radiotherapy. Our results strongly suggest that a t(1;19)(q10;p10) mediates the combined 1p/19q deletion in human gliomas. Like combined 1p/19q deletion, the 1;19 translocation is associated with superior OS and progression-free survival in low-grade glioma patients.
引用
收藏
页码:9852 / 9861
页数:10
相关论文
共 42 条
  • [1] A HUMAN ALPHOID DNA CLONE FROM THE ECORI DIMERIC FAMILY - GENOMIC AND INTERNAL ORGANIZATION AND CHROMOSOMAL ASSIGNMENT
    BALDINI, A
    SMITH, DI
    ROCCHI, M
    MILLER, OJ
    MILLER, DA
    [J]. GENOMICS, 1989, 5 (04) : 822 - 828
  • [2] MOLECULAR ANALYSIS OF CHROMOSOME-1 ABNORMALITIES IN HUMAN GLIOMAS REVEALS FREQUENT LOSS OF 1P IN OLIGODENDROGLIAL TUMORS
    BELLO, MJ
    VAQUERO, J
    DECAMPOS, JM
    KUSAK, ME
    SARASA, JL
    SAEZCASTRESANA, J
    PESTANA, A
    REY, JA
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1994, 57 (02) : 172 - 175
  • [3] CYTOGENETICS OF HUMAN BRAIN-TUMORS
    BIGNER, SH
    MARK, J
    BIGNER, DD
    [J]. CANCER GENETICS AND CYTOGENETICS, 1990, 47 (02) : 141 - 154
  • [4] Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization
    Bigner, SH
    Matthews, MR
    Rasheed, BKA
    Wiltshire, RN
    Friedman, HS
    Friedman, AH
    Stenzel, TT
    Dawes, DM
    McLendon, RE
    Bigner, DD
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (02) : 375 - 386
  • [5] Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: Efficacy and associations with chromosomal abnormalities
    Buckner, JC
    Gesme, D
    O'Fallon, JR
    Hammock, JE
    Stafford, S
    Brown, PD
    Hawkins, R
    Scheithauer, BW
    Erickson, BJ
    Levitt, R
    Shaw, EG
    Jenkins, R
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (02) : 251 - 255
  • [6] Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402
    Cairncross, Gregory
    Berkey, Brian
    Shaw, Edward
    Jenkins, Robert
    Scheithauer, Bernd
    Brachman, David
    Buckner, Jan
    Fink, Karen
    Souhami, Luis
    Laperierre, Normand
    Mehta, Minesh
    Curran, Walter
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (18) : 2707 - 2714
  • [7] Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas
    Cairncross, JG
    Ueki, K
    Zlatescu, MC
    Lisle, DK
    Finkelstein, DM
    Hammond, RR
    Silver, JS
    Stark, PC
    Macdonald, DR
    Ino, Y
    Ramsay, DA
    Louis, DN
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (19) : 1473 - 1479
  • [8] Differences in the localization and morphology of chromosomes in the human nucleus
    Croft, JA
    Bridger, JM
    Boyle, S
    Perry, P
    Teague, P
    Bickmore, WA
    [J]. JOURNAL OF CELL BIOLOGY, 1999, 145 (06) : 1119 - 1131
  • [9] DNA methylation in cancer: too much, but also too little
    Ehrlich, M
    [J]. ONCOGENE, 2002, 21 (35) : 5400 - 5413
  • [10] Oligodendroglial tumors: Refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival
    Felsberg, J
    Erkwoh, A
    Sabel, MC
    Kirsch, L
    Fimmers, R
    Blaschke, B
    Schlegel, U
    Schramm, J
    Wiestler, OD
    Reifenberger, G
    [J]. BRAIN PATHOLOGY, 2004, 14 (02) : 121 - 130