| Project/Area Number |
13670187
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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 | Iwate Medical University |
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Principal Investigator |
SUGAI Tamotu Iwate Med.univ., school of medicine, Assistant Professor, 医学部, 助教授 (20187628)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Crypt isolation method / Colorectal cancer / Loss of heterozygosity / Microsatellite instability / Tumor heterogeneiry / 腫瘍内遺伝子多様 / LOH / CIMP / 腺管分離 / 単一腺管 / 大腸腺腫 / APC / DNA ploidy / Ki-ras / MSI / p53 / Loss of heterozygisity / ATM / Genomic instability |
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| Research Abstract |
Genetic changes related to colorectal carcinomas are accumulated in individual tumor glands during disease progression. Microsatellite allelic analysis of individual tumor glands from 30 colorectal carcinomas using a polymerase chain reaction (PCR) assay coupled with crypt isolation was used to detect intratumoral genetic heterogeneity, the sequence of allelic imbalances (AIs), and the microsatellite instability (MSI) status of single tumor glands during neoplastic progression. In addition, the CpG islands methylated phenotype (CIMP) status was examined using a methylation-specific PCR method. The specimens were divided into two groups: a pooled gland sample, which was composed of more than 50 tumor glands, and a single tumor gland sample. The latter consisted of ten single tumor glands, which were obtained from the same tumor separately. Most colorectal carcinomas (27 of 30 tumors) examined were heterogeneous for at least one genetic alteration, with from two to seven genotypically different subclones detected per tumor. In 12 of the 27 heterogenous tumors, it was possible to define the order of genetic alterations during the tumor progression. By analyzing multiple single tumor glands within the same tumor, we found that various subclonal expansions were seen within the same tumors. Finally, the Al pattern of single tumor glands was not correlated with CIMP status. Most carcinomas appeared to have a heterogenous composition. This may have resulted from the successful progression of one clone that had different Ms in many chromosomal regions. This suggests that knowledge of the different genotypes of multiple single tumor glands may help to clarify the process of tumor progression.
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