2006 Fiscal Year Final Research Report Summary
Study on clonal analysis in histological heterogeneous gliomas and response to tumor therapeutics
| Project/Area Number |
17590312
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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 | Nara Medical University |
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Principal Investigator |
NAKAMURA Mitsutoshi Nara Medical University, School of Medicine, Department of Pathology, Associate Professor, 医学部, 助教授 (00305715)
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| Co-Investigator(Kenkyū-buntansha) |
KONISHI Noboru Nara Medical University, School of Medicine, Department of Pathology, Professor, 医学部, 教授 (20145832)
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| Project Period (FY) |
2005 – 2006
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| Keywords | glioblastoma / genotype / phenotype / LOH / histological heterogeneity |
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| Research Abstract |
Whereas histological heterogeneity of gliomas is well recognized, less is known of the relationship between this heterogeneity and genetic alterations. Our objective was to investigate the relationship between genotype and phenotype for markers of potential clinical utility in histologically heterogeneous gliomas. We have used laser capture microdissection to sample the various histological phenotypes present in 30 oligodendroglial tumors, 10 oligoastrocytic tumors and 50 astrocytic tumors with intratumoral histological heterogeneity.
Loss of heterogeneity (LOH) of 1p and 19q was seen only in oligodendroglial components in 26 of 30 low-grade gliomas. p53 mutation was found in 44 of 68 tumors in all astrocytic components. The low-grade gliomas in this study were more homogeneous in their genotype than their histological phenotype with regions of differing histological subtype indistinguishable by the genetic markers investigated. In 43 of 60 high-grade gliomas with intratumoral heterogeneity, identical genetic losses were present in all areas of histological differentiation, supporting the concept of clonal origin of these morphologically heterogeneous lesions. In addition, we have demonstrated genetic heterogeneity to be discernible in 17 high-grade gliomas which provides an explanation for the variety in morphological appearance of neoplastic cells. Different components of glioma may be derived from different cell clones during neoplastic transformation.
Our results suggest that low-grade gliomas are predominantly of monoclonal origin, but a subset of high-grade gliomas may be derived from different precursors. Genetic heterogeneity is discernible in high-grade gliomas, which provides an explanation for the variety in morphological appearance within the same lesion. These antecedent molecular changes may be utilized as additional molecular diagnostic criteria or prognostic markers.
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