1999 Fiscal Year Final Research Report Summary
TRKA gene induction by ATRA in neuroblastoma
| Project/Area Number |
09670850
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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 |
Pediatrics
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| Research Institution | Osaka Medical College |
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Principal Investigator |
MIYAKE Munenori Faculty of Medicine, Osaka Medical College, Research Associate, 医学部, 助手 (10268203)
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| Co-Investigator(Kenkyū-buntansha) |
MURATA Takuji Faculty of Medicine, Osaka Medical College, Research Associate, 医学部, 助手 (30288708)
ASHIDA Akira Faculty of Medicine, Osaka Medical College, Research Associate, 医学部, 助手 (80278514)
TAMAI Hiroshi Faculty of Medicine, Osaka Medical College, Professor, 医学部, 教授 (30179874)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Neuroblastoma / TRKA gene / All-trans retinoic acid / Nerve Growth Factor |
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| Research Abstract |
We have adapted the fluorescence-based detection system of the ABI automated DNA sequencer for the precise sizing and quantitation of PCR products. This system will be used to provide standardized molecular data for the prognostic assessment of primary neuroblasomas and for the detection of tumor cells in the bone marrow and the screening of peripheral stem cell harvests. Primary tumors will be evaluated for two clinically proven prognostic markers : N-myc proto-oncogene amplification and TrkA gene expression. We also demonstrate in the present proposal the heterogeneity of TrkA expression in neuroblastomas and propose that tissue-inappropriate splicing of TrkA transcripts is correlated with poor prognosis. Preliminary data are presented showing the predominant expression of TrkA I (non-neuronal isoform) in patients older than 1.5 yrs at diagnosis whereas younger patients express predominantly TrkA II (neuronal isoform) in a subgroup of histopathologically indistinguishable tumors comprising the stroma-poor, undifferentiated, low MKI Shimada class. In addition, bone marrow metastases will be detected and the tumor burden quantitated using multiple expression markers (including tyrosine hydroxylase and PGP 9.5) labeled with distinguishable fluorescent tags a multiplex RT-PCR format.
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