2000 Fiscal Year Final Research Report Summary
Molecular Genetic Analysis of Small Round Cell Sarcomas and its Application for Pathologic Differential Diagnosis
| Project/Area Number |
11670199
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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 | Kanazawa Medical University |
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Principal Investigator |
NOJIMA Takayuki Kanazawa Medical University, School of Medicine, Professor, 医学部, 教授 (50142732)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASHIMA Kazuo Hokkaido University, School of Medicine, Professor, 医学部, 教授 (50010377)
TAKEGAMI Tsutomu Kanazawa Medical University, Medical Research Institute, Professor, 総合医学研究所, 教授 (10113490)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Small round cell sarcoma / Ewing sarcoma / Synovial sarcoma / EWS gene / c-kit gene / Malignant soft tissue tumors / Gene rearrangements / Pathologic diagnosis |
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| Research Abstract |
1) Analysis on the DNA breakpoint junction of EWS/Fli1 in Ewing sarcoma group
We studied 13 cases of Ewing sarcoma by a molecular biological technique and detected the EWS/Fli1 fusion transcripts in all cases. In four cases of the examined seven, a consensus sequence, 5'-AGAAAARDRR-3' was found near the breakpoints of both genes. And sequences highly homologous to Alu repeats and/or eukaryotic topoisomerase II cleavage site were also located near the breakpoints in most of cases. These suggest that EWS/Fli1 may be specific to Ewing sarcoma group.
2) Detection of expression and mutaion of c-kit gene in small round cell tumors C-kit gene encodes a transmembrane receptor kinase which is expressed in the majority of gastrointestinal stromal tumor (GIST) and in most cases of GIST, mutations in exon 11 of c-kit were reported. We examined a juxtamembrane domain mutation of c-kit ; exon 9 to 11 in 26 cases of GIST, eight of rhabdomyosarcoma, one of neuroblastoma, nine of neurogenic tumor, and 9 of leiomyosarcoma by using RT-PCR method. Immunohistochemically, all of GIST showed positivity for c-kit, and mutaions of exon 9-11 were found in 24. Deletion and/or insertion in exon 11 were detected in 20 cases. Although none of non-GIST mesenchymal-tumor group expressed c-kit protein immunohistochemically, 7 cases of rhabdomyosarcomas, one neuroblastoma, 9 neurogenic tumors, and 7 leiomyosarcomas had mutations in exon 9-11 simillar to those of GIST.Furthermore, abnormalities in exon 11 were found in 5 cases, one, 5, and 3, respectively. These findings of the similarity between GIST group and non-GIST mesenchymal-tumor group is suggested to be the same mechanism of carcinogenesis in small round cell tumors.
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