2004 Fiscal Year Final Research Report Summary
Genome-wide analysis of intratumoral heterogeneity in genomic copy number and expression pattern.
| Project/Area Number |
15590301
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
SUGIHARA Hiroyuki Shiga University of Medical Science, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30171169)
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| Co-Investigator(Kenkyū-buntansha) |
MUKAISHO Ken-ichi Shiga University of Medical Science, Faculty of Medicine, Research Assistant, 医学部, 助手 (50343223)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Gastric carcinoma / Laser microdissection / DOP-PCR / CGH / cDNA microarray / CESH / Intratumoral heterogeneity |
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| Research Abstract |
This study focused on the problems ; to what extent the regional heterogeneity of the gene expression pattern is ascribed to the regional changes in genomic copy number and to what extent the gene expression pattern of the deep invasion is inferred from the mucosal biopsy specimen.
Using gastric carcinoma(GC) cell lines and primary esophageal and gastric carcinomas, we carried out comparative genome-wide analyses of the transcription pattern and the genomic copy number at the chromosome level, which were determined by comparative expressed sequence hybridization(CESH) and comparative genomic hybridization(CGH), respectively. We firstly established the methodology of CESH that showed better concordance with the results of cDNA microarray by modifying the methods of probe labeling and those of signal amplification. We found that the concordance with CDNA microarray was higher in T7 amplification and pre-cDNA labeling than in the DOP-PCR amplification/labeling that was previously used for
… More
CESH.
Secondly, using two cell lines deriving from undifferentiated-type GC, we demonstrated that gene expression was often up/down-regulated in clustered genes in certain chromosomal loci that can be detected by CESH as well as cDNA microarray and that these expression changes may have resulted either from genomic copy number changes or from transcriptional regulation. Thirdly, using multiple samples from individual primary GCs and esophageal cancers, the stemline copy-number changes that were consistently detected in multiple samples were mostly found to accompany up/down-regulation of the corresponding chromosomal segments. About 50% of stemline up/down-regulations were accompanied by genomic copy number changes, whereas heterogeneous up/down-regulations were infrequently accompanied by the genomic changes.
These findings suggest that we may infer the gene expression pattern in the deeper part of the tumor from that in the mucosa only in the chromosomal regions of stemline changes that are determined from multiple mucosal samples. Less
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Research Products
(10 results)
