Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas.
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 approximately 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.


CONCLUSIONS
Our data implicate a role of BCCIP in astrocytic tumorigenesis, and lack of BCCIP may be used as a marker for astrocytomas.
Liu
Jingmei
J
Department of Radiation Oncology, The Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. liuj8@umdnj.edu
Lu
Huimei
H
Ohgaki
Hiroko
H
Merlo
Adrian
A
Shen
Zhiyuan
Z
D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
C415366:BCCIP protein, human; D024682:BRCA2 Protein; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins