1997 Fiscal Year Final Research Report Summary
The development of rapid diagnostic system for detecting a predisposition to cancer in early childhood
| Project/Area Number |
07557232
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pediatrics
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| Research Institution | University of Tokyo |
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Principal Investigator |
HAYASHI Yasuhide Univ.of Tokyo, Faculty of Medicine, Associate Professor, 医学部・附属病院, 講師 (30238133)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMORI Shunji Mitsubishi Biochemical Cooperation, Molecular Department, Director, 遺伝子解析部, 部長
KOBAYASHI Miyuki Univ.of Tokyo, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 助手 (60205391)
YANAGISAWA Masayoshi Univ.of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 助手 (90049031)
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| Project Period (FY) |
1995 – 1997
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| Keywords | acute lymphoblastic leukemia / neuroblastoma / tumor suppressor gene / p53 gene / RAS gene / p16 gene / p73 gene / p19 gene |
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| Research Abstract |
Homozygous deletions (HD) of p16 and p15 genes and mutations of pl6, RAS and p53 genes were examined in acute lymphoblastic leukemia (ALL) and childhood solid tumors. Rearrangements of p16 were higher in cell lines and fresh leukemia without t(1 ; 19) than those with t(l ; 19). Remarkably, mutations were found in 3 of the primary cases (5%). As for leukemia with MLL rearrangement (MLL+), HD of the p16 and p15 genes was found in 5 (11%) of 19 acute myeloid leukemias (AMLs). PCR-single strand conformation polymorphism (SSCP) showed no mutation in the 32 patients tested. Our results suggest that alterations of 16 and p15 genes are involved in a subset of acute leukemias with MLL.Mutations of the p53 gene were found in 3 of 57 (5%) T-ALL patients at diagnosis, 1 of 14 (7%) patients at relapse and in 12 of 18 (67%) cell lines, All patients with p53 mutations in the course of disease died. Mutations of the p21 gene were not identified in 71 fresh samples and in 18 cell lines. N-RAS mutations
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were found in 2 of 57 (4%) fresh T-ALL patients only at diagnosis, and 4 of 118 cell lines (22%). Alterations of the p16 gene were found in 18 of 47(38%) patients at diagnosis and in 7 of 14(50%) at relapse (not significant). There were no differences in the frequency of alteration of the p16 and p15 genes between event-free patients and the remaining patients. Furthermore, we found the methylation of p16 gene in 3 of 7 patients lacking homozygous deletions, suggesting higher frequency of p16 inactivation than previous reports in T-ALL.
N-myc, p16, DCC, DPC4, MADR2 and p73 genes were analyzed in neuroblastoma (NB). HD of p16 genre was not found in 81 samples. PCR-SSCP analysis identified only missense mutation, suggesting polymorphism. Absence or decreased expression of pl6 gene was found in 6 of 10 cell lines. Hypermethylation of the p16 gene was found in 12 of 19 cell lines, suggesting that hypermethylation plays an important role for the development or progression of neuroblastoma. Absence or reduced expression of DCC gene was found in half of the samples. PCR-SSCP analysis of DCC gene showed only missense mutation, suggesting polymorphism. Alterations of DPC4 and MDRR2 genes were relatively rare. These results suggest that DCC gene plays an important role in the dissemination of NB, and that DPC4 and MAD2 gene are not involved in the development of NB.This study may counribute to the development of rapid diagnostic system for detecting a predisposition to cancer in early childhood. Less
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[Publications] Kawamura M,Kikuchi A,Kobayashi S,Hanada R,Yamamoto K,Horibe H,Shikano T,Ueda K,Hayashi K,Sekiya T,Hayashi Y: "Mutations of the p53 and ras genes in childhood t (1 ; 19) -acute lymphoblastic leukemia" Blood. 85. 2546-2552 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ohnishi H,Guo SX,Ida K,Taki T,Naritaka S,Bessho F,Yanagisawa M,Hanada R,Eguchi M,Kamada N,Kita K,Yamamori S,Hayashi Y.: "Alteration of pl6 and pl5 genes in acute leukemia with MLL gene rearrangements and thier corelation with clinical features." Leukemia. 11. 2120-2124 (1997)
Description
「研究成果報告書概要(欧文)」より
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