Alterations o f C hromosome A rms 1 p a nd 1 9q a s P redictors of S urvival i n O ligodendrogliom as, A strocytomas, a nd Mixed O ligoastrocytoma s

Purpose: A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy. We set out to further clarify the diagnostic and prognostic implications of these alterations in a broader set of diffuse gliomas, including astrocytic neoplasms and low-grade oligodendrogliomas. Patients and Methods: Fluorescence in situ hybridization (FISH) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas), collected as part of an ongoing prospective investigation of CNS tumors. Results: The oligodendroglial phenotype was highly associated with loss of 1p (P 5 .0002), loss of 19q (P < .0001), and combined loss of 1p and 19q (P < .0001). Combined loss of 1p and 19q was identified as a univariate predictor of prolonged overall survival among patients with pure oligodendroglioma (logrank, P 5 .03) and remained a significant predictor after adjusting for the effects of patient age and tumor grade (P < .01). This favorable association was not evident in patients with astrocytoma or mixed oligoastrocytoma. Conclusion: Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma, independent of tumor grade. Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas, a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management. J Clin Oncol 18:636-645. © 2000 by American Society of Clinical Oncology.

[1]  B. Scheithauer,et al.  Detection of p16, RB, CDK4, and p53 gene deletion and amplification by fluorescence in situ hybridization in 96 gliomas. , 1999, American journal of clinical pathology.

[2]  D. Louis,et al.  The human glia maturation factor-gamma gene: genomic structure and mutation analysis in gliomas with chromosome 19q loss , 1999, Neurogenetics.

[3]  B. Scheithauer,et al.  Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype , 1999, Oncogene.

[4]  D. Louis,et al.  Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. , 1998, Journal of the National Cancer Institute.

[5]  W. Liu,et al.  Genomic organization and mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions. , 1998, Genomics.

[6]  D. Bostwick,et al.  A molecular cytogenetic analysis of 7q31 in prostate cancer. , 1997, Cancer research.

[7]  D. Louis,et al.  Molecular Genetic Evidence for Subtypes of Oligoastrocytomas , 1997, Journal of neuropathology and experimental neurology.

[8]  G. Mohapatra,et al.  Detection of p16 Gene Deletions in Gliomas: A Comparison of Fluorescence in Situ Hybridization (FISH) Versus Quantitative PCR , 1997, Journal of neuropathology and experimental neurology.

[9]  A. Yang,et al.  Monoallelically Expressed Gene Related to p53 at 1p36, a Region Frequently Deleted in Neuroblastoma and Other Human Cancers , 1997, Cell.

[10]  L. Rorke Pathologic diagnosis as the gold standard , 1997, Cancer.

[11]  D. Louis,et al.  Refined deletion mapping of the chromosome 19q glioma tumor suppressor gene to the D19S412-STD interval. , 1996, Oncogene.

[12]  D. Louis,et al.  Procarbazine, lomustine, and vincristine (PCV) chemotherapy for grade III and grade IV oligoastrocytomas. , 1996, Journal of neurosurgery.

[13]  M. Schwab,et al.  Genomic instability in Ip and human malignancies , 1996, Genes, chromosomes & cancer.

[14]  D. Louis,et al.  The BAX gene maps to the glioma candidate region at 19q13.3, but is not altered in human gliomas. , 1996, Cancer genetics and cytogenetics.

[15]  G. Krol,et al.  Low-grade oligodendroglioma responds to chemotherapy , 1996, Neurology.

[16]  D. Louis,et al.  A tiger behind many doors: multiple genetic pathways to malignant glioma. , 1995, Trends in genetics : TIG.

[17]  D. Louis,et al.  Cloning of a highly conserved human protein serine-threonine phosphatase gene from the glioma candidate region on chromosome 19q13.3. , 1995, Genomics.

[18]  J. Rey,et al.  Allelic loss at 1p and 19q frequently occurs in association and may represent early oncogenic events in oligodendroglial tumors , 1995, International journal of cancer.

[19]  V. Ganju,et al.  Region‐specific loss of heterozygosity on chromosome 19 is related to the morphologic type of human glioma , 1995, Genes, chromosomes & cancer.

[20]  F. Waldman,et al.  Chromosomal abnormalities in glioblastoma multiforme tumors and glioma cell lines detected by comparative genomic hybridization , 1995, International journal of cancer.

[21]  D. Louis,et al.  Shared Allelic Losses on Chromosomes 1p and 19q Suggest a Common Origin of Oligodendroglioma and Oligoastrocytoma , 1995, Journal of neuropathology and experimental neurology.

[22]  T. Cascino,et al.  Chemotherapy for anaplastic oligodendroglioma. National Cancer Institute of Canada Clinical Trials Group. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  D. Lenartz,et al.  Deletion mapping of chromosome 19 in human gliomas , 1994, International journal of cancer.

[24]  R. Wellenreuther,et al.  Loci associated with malignant progression in astrocytomas: a candidate on chromosome 19q. , 1994, Cancer research.

[25]  B. Scheithauer,et al.  Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  P. Kelly,et al.  Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo‐astrocytomas , 1992, Genes, Chromosomes and Cancer.

[27]  I. Petersen,et al.  Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas. , 1992, Cancer research.

[28]  David W. Smith,et al.  The treatment of oligodendrogliomas and mixed oligodendroglioma-astrocytomas with PCV chemotherapy. , 1992, Journal of neurosurgery.

[29]  A. Kiss,et al.  Abnormalities of chromosome 1 in relation to human malignant diseases. , 1989, Cancer genetics and cytogenetics.

[30]  J. Cairncross,et al.  Successful chemotherapy for recurrent malignant oligodendroglioma , 1988, Annals of neurology.

[31]  N. B. Atkin Chromosome 1 aberrations in cancer. , 1986, Cancer genetics and cytogenetics.

[32]  O. G. Dodge,et al.  Histological Typing of tumours of the Central Nervous System , 1981, British Journal of Cancer.

[33]  N. Mantel Evaluation of survival data and two new rank order statistics arising in its consideration. , 1966, Cancer chemotherapy reports.

[34]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[35]  C. Junien,et al.  Report of the committee on chromosome and gene loss in human neoplasia , 1991 .

[36]  D. Cox Regression Models and Life-Tables , 1972 .