Comprehensive Allelotype and Genetic Analysis of 466 Human Nervous System Tumors

Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2, and PTEN genes were analyzed in addition. Our data point to several novel genetic loci associated with brain tumor development, demonstrate relationships between molecular changes and histopathological features, and further expand the concept of molecular tumor variants in neuro-oncology. This catalogue may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors.

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

[2]  D. Louis,et al.  PTEN mutations in gliomas and glioneuronal tumors , 1998, Oncogene.

[3]  K. Sasaki,et al.  Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization , 1998, Genes, chromosomes & cancer.

[4]  M. Prados,et al.  Genetic analysis of glioblastoma multiforme provides evidence for subgroups within the grade , 1998, Genes, chromosomes & cancer.

[5]  R. Wellenreuther,et al.  Analysis of the PTEN gene in human meningiomas , 1998, Neuropathology and applied neurobiology.

[6]  K. Plate,et al.  p53 Mutations versus EGF Receptor Expression in Giant Cell Glioblastomas , 1997, Journal of neuropathology and experimental neurology.

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

[8]  G. Reifenberger,et al.  Molecular genetic analysis of giant cell glioblastomas. , 1997, The American journal of pathology.

[9]  Jan Mollenhauer,et al.  DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3–26.1 is deleted in malignant brain tumours , 1997, Nature Genetics.

[10]  D. Louis,et al.  Association of EGFR Gene Amplification and CDKN2 (p16/MTS1) Gene Deletion in Glioblastoma Multiforme , 1997, Brain pathology.

[11]  W. K. Alfred Yung,et al.  Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers , 1997, Nature Genetics.

[12]  M. Wigler,et al.  PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer , 1997, Science.

[13]  W. B. Smith,et al.  A Role for Endothelial NO Synthase in LTP Revealed by Adenovirus-Mediated Inhibition and Rescue , 1996, Science.

[14]  C. Sommer,et al.  Characterization of genomic alterations associated with glioma progression by comparative genomic hybridization. , 1996, Oncogene.

[15]  B. Scheithauer,et al.  The Glial and Mesenchymal Elements of Gliosarcomas Share Similar Genetic Alterations , 1996, Journal of neuropathology and experimental neurology.

[16]  D. Louis,et al.  Amplification of the cyclin-dependent kinase 4 (CDK4) gene is associated with high cdk4 protein levels in glioblastoma multiforme , 1996, Acta Neuropathologica.

[17]  A. von Deimling,et al.  A Polymerase Chain Reaction‐based Assay for the Rapid Detection of Gene Amplification in Human Tumors , 1996, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[18]  G. Woude,et al.  Abnormal Centrosome Amplification in the Absence of p53 , 1996, Science.

[19]  I. Petersen,et al.  Evidence for a novel tumor suppressor gene on chromosome 15 associated with progression to a metastatic stage in breast cancer. , 1996, Oncogene.

[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]  C. James,et al.  CDK4 amplification is an alternative mechanism to p16 gene homozygous deletion in glioma cell lines. , 1994, Cancer research.

[23]  D. Louis,et al.  MTS1/CDKN2 gene mutations are rare in primary human astrocytomas with allelic loss of chromosome 9p. , 1994, Human molecular genetics.

[24]  P. Meltzer,et al.  Amplification of multiple genes from chromosomal region 12q13-14 in human malignant gliomas: preliminary mapping of the amplicons shows preferential involvement of CDK4, SAS, and MDM2. , 1994, Cancer research.

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

[26]  A. von Deimling,et al.  A device for processing large acrylamide gels. , 1994, BioTechniques.

[27]  Olivier Delattre,et al.  Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas , 1994, Nature Genetics.

[28]  D. Louis,et al.  A rapid and non‐radioactive PCR based assay for the detection of allelic loss in human gliomas , 1993, Neuropathology and applied neurobiology.

[29]  D. Louis,et al.  Subsets of Glioblastoma Multiforme Defined by Molecular Genetic Analysis , 1993, Brain pathology.

[30]  D. Pinkel,et al.  Comparative Genomic Hybridization for Molecular Cytogenetic Analysis of Solid Tumors , 2022 .

[31]  D. Louis,et al.  A (CA)n dinucleotide repeat assay for evaluating loss of allelic heterozygosity in small and archival human brain tumor specimens. , 1992, The American journal of pathology.

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

[33]  I. Petersen,et al.  Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. , 1992, Journal of neurosurgery.

[34]  I. Petersen,et al.  p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. , 1992, Cancer research.

[35]  C. James,et al.  Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[36]  P. Kleihues,et al.  p53 mutations in nonastrocytic human brain tumors. , 1991, Cancer research.

[37]  V. P. Collins,et al.  Molecular genetic analysis of chromosome 22 in 81 cases of meningioma. , 1990, Cancer research.

[38]  Y. Nakamura,et al.  Loss of heterozygosity for loci on chromosome 17p in human malignant astrocytoma. , 1989, Cancer research.

[39]  Y. Nakamura,et al.  Allelotype of colorectal carcinomas. , 1989, Science.

[40]  C. James,et al.  Mitotic recombination of chromosome 17 in astrocytomas. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[41]  C. James,et al.  Clonal genomic alterations in glioma malignancy stages. , 1988, Cancer research.

[42]  V. P. Collins,et al.  Deletion mapping of a locus on human chromosome 22 involved in the oncogenesis of meningioma. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[43]  R. Martuza,et al.  Molecular genetic approach to human meningioma: loss of genes on chromosome 22. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Hermona Soreq,et al.  Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin , 1985, Nature.

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

[46]  E. B. Jackson,et al.  Effects of Colchicine and Radiation on Growth of Normal Tissues and Tumors , 1940 .

[47]  J. Cairncross,et al.  Gliomas in families: chromosomal analysis by comparative genomic hybridization. , 1998, Cancer genetics and cytogenetics.

[48]  D. Lenartz,et al.  Analysis of the neurofibromatosis 2 gene reveals molecular variants of meningioma. , 1995, The American journal of pathology.

[49]  B. Scheithauer,et al.  Histological Typing of Tumours of the Central Nervous System , 1993, World Health Organization.