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Chromosome Replicating Timing Combined with Fluorescent In situ Hybridization
Published on: December 10, 2012
Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path
K Ichimura1, A J Mungall, H Fiegler
1Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. ki212@cam.ac.uk
Abstract:
Deletions of chromosome 6 are a common abnormality in diverse human malignancies including astrocytic tumours, suggesting the presence of tumour suppressor genes (TSG). In order to help identify candidate TSGs, we have constructed a chromosome 6 tile path microarray. The array contains 1,780 clones (778 P1-derived artificial chromosome and 1,002 bacterial artificial chromosome) that cover 98.3% of the published chromosome 6 sequences. A total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30 anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using this array. Single copy number change was successfully detected and the result was in general concordant with a microsatellite analysis. The pattern of copy number change was complex with multiple interstitial deletions/gains. However, a predominance of telomeric 6q deletions was seen. Two small common and overlapping regions of deletion at 6q26 were identified. One was 1,002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, ARID1B. The data show that the chromosome 6 tile path array is useful in mapping copy number changes with high resolution and accuracy. We confirmed the high frequency of chromosome 6 deletions in AA and GB, and identified two novel commonly deleted regions that may harbour TSGs.
Insights
Chromosome 6 deletions are frequent in brain tumors like anaplastic astrocytomas and glioblastomas. Researchers identified two new deleted regions on chromosome 6q26, potentially harboring tumor suppressor genes.
Area of Science:
- Oncology
- Genetics
- Genomics
Background:
- Chromosome 6 deletions are common in human cancers, particularly astrocytic tumors.
- These deletions suggest the presence of critical tumor suppressor genes (TSGs).
Purpose of the Study:
- To identify candidate tumor suppressor genes by analyzing chromosome 6 deletions in adult astrocytic tumors.
- To develop and utilize a high-resolution chromosome 6 tile path microarray for precise deletion mapping.
Main Methods:
- Construction of a chromosome 6 tile path microarray containing 1,780 clones covering 98.3% of chromosome 6 sequences.
- Analysis of 104 adult astrocytic tumors (diffuse astrocytomas, anaplastic astrocytomas, glioblastomas) using the microarray.
- Detection of single copy number changes and comparison with microsatellite analysis.
Main Results:
- The chromosome 6 tile path microarray accurately mapped copy number changes with high resolution.
- A predominance of telomeric 6q deletions was observed in the analyzed tumors.
- Two novel, small, overlapping common deletion regions at 6q26 were identified, harboring genes including PACRG, QKI, and ARID1B.
Conclusions:
- The chromosome 6 tile path microarray is a valuable tool for high-resolution deletion mapping in cancer research.
- Chromosome 6 deletions are highly frequent in anaplastic astrocytomas and glioblastomas.
- The identified novel deleted regions at 6q26 are strong candidates for harboring tumor suppressor genes involved in astrocytoma development.
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