GOA, a novel gene encoding a ring finger B-box coiled-coil protein, is overexpressed in astrocytoma.

Serial analysis of gene expression (SAGE) was used to identify a gene named GOA (gene overexpressed in astrocytoma), which codes for a novel Ring finger B-box coiled-coil (RBCC) protein. Northern blot hybridization showed overexpression of GOA in 9 of 10 astrocytomas. Except for kidney, in which high expression was found, expression levels in normal tissues were low and comparable to normal brain. Immunohistochemistry demonstrated presence of GOA, with prominent nuclear staining, in astrocytoma tumor cells and astrocytes of fetal brain, but virtual absence in mature astrocytes. Overexpression was not due to amplification, since amplification of GOA was only found in one of 65 astrocytomas. GOA was localized to 17q24-25, a region that is frequently gained or amplified in a number of other tumor types. GOA contains two LXXLL motifs, which are thought to be important for nuclear receptor binding. Our data suggest an important role of GOA in the process of dedifferentiation that is associated with astrocytoma tumorigenesis and possibly with that of other tumor types as well.

[1]  S. Knuutila,et al.  DNA sequence copy number changes in gastrointestinal stromal tumors: tumor progression and prognostic significance. , 2000, Cancer research.

[2]  S. Petersen,et al.  Chromosomal Imbalances in Brain Metastases of Solid Tumors , 2000, Brain pathology.

[3]  P. Lichter,et al.  Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high‐level amplifications , 2000, Genes, chromosomes & cancer.

[4]  C. Theillet,et al.  17q21-q25 aberrations in breast cancer: combined allelotyping and CGH analysis reveals 5 regions of allelic imbalance among which two correspond to DNA amplification , 1999, Oncogene.

[5]  P M Bossuyt,et al.  Genes differentially expressed in medulloblastoma and fetal brain. , 1999, Physiological genomics.

[6]  D. Bigner,et al.  Molecular pathogenesis of malignant gliomas. , 1999, Current opinion in oncology.

[7]  F. Slack,et al.  A novel repeat domain that is often associated with RING finger and B-box motifs. , 1998, Trends in biochemical sciences.

[8]  P. Pontarotti,et al.  B30.2-like domain proteins: update and new insights into a rapidly expanding family of proteins. , 1998, Molecular biology and evolution.

[9]  M. Wolter,et al.  Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[10]  L. Etkin,et al.  Characterization and function of Xnf7 during early development of Xenopus , 1997, Journal of cellular physiology.

[11]  David M. Heery,et al.  A signature motif in transcriptional co-activators mediates binding to nuclear receptors , 1997, Nature.

[12]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[13]  K. Kinzler,et al.  Serial Analysis of Gene Expression , 1995, Science.

[14]  P. Chambon,et al.  The N‐terminal part of TIF1, a putative mediator of the ligand‐dependent activation function (AF‐2) of nuclear receptors, is fused to B‐raf in the oncogenic protein T18. , 1995, The EMBO journal.

[15]  S. Leenstra,et al.  Amplification of the anonymous marker D17S67 in malignant astrocytomas , 1994, Genes, chromosomes & cancer.

[16]  Y. Ouchi,et al.  Genomic binding-site cloning reveals an estrogen-responsive gene that encodes a RING finger protein. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[17]  P. Freemont,et al.  A novel zinc finger coiled-coil domain in a family of nuclear proteins. , 1992, Trends in biochemical sciences.

[18]  Christine Chomienne,et al.  The PML-RARα fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR , 1991, Cell.

[19]  H. Hiai,et al.  Developmentally regulated expression of a human "finger"-containing gene encoded by the 5' half of the ret transforming gene , 1988, Molecular and cellular biology.

[20]  A. Sehgal Molecular changes during the genesis of human gliomas. , 1998, Seminars in surgical oncology.