Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas

被引：24
作者：
Liu J. [1 ]
Lu H. [1 ]
Ohgaki H. [2 ]
Merlo A. [3 ]
Shen Z. [1 ]
机构：
[1] Department of Radiation Oncology, The Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903
[2] Pathology Group, International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08
[3] Neurosurgery and Laboratory of Molecular Neuro-Oncology, Departments of Surgery and Research, University Hospitals, CH-4031 Basel
来源：
BMC Cancer | / 9卷 / 1期
基金：
美国国家卫生研究院;
关键词：
Brain Tumor; Astrocytoma; Glial Fibrillary Acid Protein; Astrocytic Tumor; Brain Tumor Survival;
D O I：
10.1186/1471-2407-9-268
中图分类号：
学科分类号：
摘要：
Background: Loss of heterozygosity of chromosome 10q26 has been shown to be associated with the aggressiveness of astrocytic tumors (or astrocytomas), but the responsible gene(s) residing in this region has not been fully identified. The BCCIP gene is located at chromosome 10q26. It encodes a BRCA2 and CDKN1A (p21) interacting protein. Previous studies have shown that down-regulation of BCCIP impairs recombinational DNA repair, G1/S cell cycle checkpoint, p53 trans-activation activity, cytokinesis, and chromosome stability, suggesting a potential role of BCCIP in cancer etiology. In this study, we investigated whether BCCIP is altered in astrocytomas. Methods: Genomic DNA from 45 cases of grade IV astrocytic tumor (glioblastoma) tissues and 12 cases of normal tissues were analyzed by quantitative PCR. The BCCIP protein expression in 96 cases of grade II-IV astrocytic tumors was detected by immunohistochemistry (IHC). IHC staining of glial fibrillary acid protein (GFAP), a marker for astrocytic cells, was used to identify cells of the astrocytic lineage. Results: We found that BCCIP protein is expressed in normal cells with positive staining of GFAP. However, BCCIP protein expression was not detectable in ∼45% of all astrocytic tumors, and in > 60% in the grade IV glioblastoma. About 45% glioblastoma have significant (p < 0.01) reduction of BCCIP gene copy number when compared to normal DNA. Furthermore, the frequency of lacking BCCIP expression is associated with the aggressiveness of astrocytic tumors. Conclusion: Our data implicate a role of BCCIP in astrocytic tumorigenesis, and lack of BCCIP may be used as a marker for astrocytomas. © 2009 Liu et al; licensee BioMed Central Ltd.
引用
收藏
相关论文
共 55 条
[1]  
Rasheed B.K., Fuller G.N., Friedman A.H., Bigner D.D., Bigner S.H., Loss of heterozygosity for 10q loci in human gliomas, Genes Chromosomes Cancer, 5, pp. 75-82, (1992)
[2]  
Karlbom A.E., James C.D., Boethius J., Cavenee W.K., Collins V.P., Nordenskjold M., Larsson C., Loss of heterozygosity in malignant gliomas involves at least three distinct regions on chromosome 10, Hum Genet, 92, pp. 169-174, (1993)
[3]  
Balesaria S., Brock C., Bower M., Clark J., Nicholson S.K., Lewis P., de Sanctis S., Evans H., Peterson D., Mendoza N., Et al., Loss of chromosome 10 is an independent prognostic factor in high-grade gliomas, Br J Cancer, 81, pp. 1371-1377, (1999)
[4]  
Steck P.A., Lin H., Langford L.A., Jasser S.A., Koul D., Yung W.K., Pershouse M.A., Functional and molecular analyses of 10q deletions in human gliomas, Genes Chromosomes Cancer, 24, pp. 135-143, (1999)
[5]  
Fujisawa H., Reis R.M., Nakamura M., Colella S., Yonekawa Y., Kleihues P., Ohgaki H., Loss of heterozygosity on chromosome 10 is more extensive in primary (de novo) than in secondary glioblastomas, Lab Invest, 80, pp. 65-72, (2000)
[6]  
Daido S., Takao S., Tamiya T., Ono Y., Terada K., Ito S., Ouchida M., Date I., Ohmoto T., Shimizu K., Loss of heterozygosity on chromosome 10q associated with malignancy and prognosis in astrocytic tumors, and discovery of novel loss regions, Oncol Rep, 12, pp. 789-795, (2004)
[7]  
Hill C., Hunter S.B., Brat D.J., Genetic markers in glioblastoma: Prognostic significance and future therapeutic implications, Adv Anat Pathol, 10, pp. 212-217, (2003)
[8]  
Ohgaki H., Genetic pathways to glioblastomas, Neuropathology, 25, pp. 1-7, (2005)
[9]  
Ohgaki H., Dessen P., Jourde B., Horstmann S., Nishikawa T., Di Patre P.L., Burkhard C., Schuler D., Probst-Hensch N.M., Maiorka P.C., Et al., Genetic pathways to glioblastoma: A population-based study, Cancer Res, 64, pp. 6892-6899, (2004)
[10]  
Merlo A., Genes and pathways driving glioblastomas in humans and murine disease models, Neurosurg Rev, 26, pp. 145-158, (2003)
123456