1996 Fiscal Year Annual Research Report

癌になりやすい体質の小児期における簡易診断システムの開発

Research Project

Project/Area Number	07557232
Section	試験
Research Institution	The University of Tokyo
Principal Investigator	林泰秀東京大学, 医学部・附属病院, 講師 (30238133)
Co-Investigator(Kenkyū-buntansha)	山森俊治三菱化学BCL社, 遺伝子解析部, 部長小林茂俊東京大学, 医学部・附属病院, 助手 (70260487) 森脇浩一東京大学, 医学部・附属病院, 助手 (10251274) 小林美由紀東京大学, 医学部・附属病院, 助手 (60205391) 柳澤正義東京大学, 医学部・附属病院, 教授 (90049031)
Keywords	白血病 / 固形腫瘍 / 癌抑制遺伝子 / P53遺伝子 / P16遺伝子 / DCC遺伝子 / PCR-SSCP
Research Abstract	9p21領域から単離された(p16/MTS1/CDKN2遺伝子)遺伝子は、多数の癌でホモ接合体欠失(HD)が報告され注目されている。今年度は小児白血病と固形腫瘍におけるp16遺伝子の異常の意義を検討した。T-ALLでは、新鮮白血病56例中26例(46%)、細胞株17株中12株(71%)にp16遺伝子の異常がみられ、このうちHDはそれぞれ22例(39%)、10株(59%)にみられ、最終的にstop codonとなっていた。B前駆型-ALLでは、初診時45例中11例(24%)、再発時22例中5例(23%)、細胞株15株中11株(74%)でHDを認め、これらの症例はHDのない症例と比較して予後に有意差はみられなかった。これまでB-前駆型ALLでは1例のみ点変異が報告されていたが、我々は新鮮白血病45例中3例、細胞株15株中2株に変異を認めた。さらに、神経芽腫15株と40例、ユ-イング肉腫7株と15例、横紋筋肉腫3株と20例でp16遺伝子の検討を行ったが、いずれにおいてもHDはみられなかったが、ウエスタンプロッティングにより神経芽腫19株中13株、ユ-イング肉腫7株中3株に蛋白質の発現の消失がみられ、p16遺伝子のこれらの腫瘍の発症への関与が示唆された。DCC遺伝子の検討では、神経芽腫15株中10株、腫瘍20例中8例に発現の減弱または消失がみられ、PCR-SSCP法で5例の変異を見いだした。DPC4とMADR2遺伝子の発現は神経芽腫ではそれぞれ7株中2株、7株中1株に消失がみられたが、点変異はみられなかった。さらに新しく見いだされた癌抑制遺伝子の検討を行う予定である。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Tomohiko Taki: "Fusion of the MLL gene with two differeut geues,AF6 and AF-5α,by a complex translocation involving chromosomes 5,6,8 and 11 in intant leukemia" Oncogene. 13. 2121-2130 (1996)
[Publications] Shigetoshi Kobayashi: "Mutations of the Btk gene in twelve unrelated families with X-linked agdmmaglobulinemia in Japan:Immunological phenctypes aie inconsistent with the location of the mutations" Human Genetics. 97. 424-430 (1996)
[Publications] Hiroaki Ohnishi: "Infrequent mutations of the p53 gene in hepatoblastomas" Gene Chromosomes Cancer. 15. 187-190 (1996)
[Publications] Hiroaki Ohnishi: "Homozygous deletions of p16/MTS1 and P15/MTS2 genes in t(1;19)-negative but not in t(1;19)-positive B precursor acute lymphoblastic leukemia in childhood" Leukemia. 10. 1104-1110 (1996)
[Publications] Tomohiko Taki: "Frequency and clinical significance of the MLL gene rearrangemongts in infant acute lenkemia." Leukemia. 10. 1303-1307 (1996)
[Publications] Kakuda: "A novel human leukaemic cell line,CTS,has a t(6;11)chromosomal translocation and characteristics of pluripotent stem cells." British Journal of Haematology. 95. 306-318 (1996)
[Publications] Yoshiaki Tsuchida: "Genetic clinical markers of human neuroblastomd with special reference to N-myc oncogene:Amplified or not amplitied?-Overview" Tumor Biology. 17. 65-74 (1996)
[Publications] Akira Inoue: "Competitive polymerase chain reaction for the quantification of N-myc gene number in neuroblastomd" Tumor Biology. 17. 262-270 (1996)
[Publications] Atushi Ohshima: "11q23 aberation is an additional chromosomal change in de movo acute leukemia after treatment with Etoposido and mitoxantrono." American Journal of Hematology. 53. 264-266 (1996)
[Publications] Junko Takita: "Deletion map of chromosome 9 and p16(CDKN2A)gene alterations in neuroblastoma." Cancer Research. 1997年4月(発表予定). (1997)
[Publications] Kohmei Ida: "Detection of chimeric mRNA by reverse transcriptase chain reaction for diagnosis and monitoring of acuto/eukemias with 11q23 abnormalities" Medical Pediatric Oncology. (in press).
[Publications] Hirofumi Kobayashi: "Inversion of chromosome 11,inV(11)(p15q22)as a recurring chromosomal aberration associated with denovo and secondary myeloid malignancies." Gene Chromosomes Cancer. (in press).

1996 Fiscal Year Annual Research Report

癌になりやすい体質の小児期における簡易診断システムの開発

Principal Investigator

林 泰秀 東京大学, 医学部・附属病院, 講師 (30238133)

Research Products

[Publications] Tomohiko Taki: "Fusion of the MLL gene with two differeut geues,AF6 and AF-5α,by a complex translocation involving chromosomes 5,6,8 and 11 in intant leukemia" Oncogene. 13. 2121-2130 (1996)

[Publications] Shigetoshi Kobayashi: "Mutations of the Btk gene in twelve unrelated families with X-linked agdmmaglobulinemia in Japan:Immunological phenctypes aie inconsistent with the location of the mutations" Human Genetics. 97. 424-430 (1996)

[Publications] Hiroaki Ohnishi: "Infrequent mutations of the p53 gene in hepatoblastomas" Gene Chromosomes Cancer. 15. 187-190 (1996)

[Publications] Hiroaki Ohnishi: "Homozygous deletions of p16/MTS1 and P15/MTS2 genes in t(1;19)-negative but not in t(1;19)-positive B precursor acute lymphoblastic leukemia in childhood" Leukemia. 10. 1104-1110 (1996)

[Publications] Tomohiko Taki: "Frequency and clinical significance of the MLL gene rearrangemongts in infant acute lenkemia." Leukemia. 10. 1303-1307 (1996)

[Publications] Kakuda: "A novel human leukaemic cell line,CTS,has a t(6;11)chromosomal translocation and characteristics of pluripotent stem cells." British Journal of Haematology. 95. 306-318 (1996)

[Publications] Yoshiaki Tsuchida: "Genetic clinical markers of human neuroblastomd with special reference to N-myc oncogene:Amplified or not amplitied?-Overview" Tumor Biology. 17. 65-74 (1996)

[Publications] Akira Inoue: "Competitive polymerase chain reaction for the quantification of N-myc gene number in neuroblastomd" Tumor Biology. 17. 262-270 (1996)

[Publications] Atushi Ohshima: "11q23 aberation is an additional chromosomal change in de movo acute leukemia after treatment with Etoposido and mitoxantrono." American Journal of Hematology. 53. 264-266 (1996)

[Publications] Junko Takita: "Deletion map of chromosome 9 and p16(CDKN2A)gene alterations in neuroblastoma." Cancer Research. 1997年4月(発表予定). (1997)

[Publications] Kohmei Ida: "Detection of chimeric mRNA by reverse transcriptase chain reaction for diagnosis and monitoring of acuto/eukemias with 11q23 abnormalities" Medical Pediatric Oncology. (in press).

[Publications] Hirofumi Kobayashi: "Inversion of chromosome 11,inV(11)(p15q22)as a recurring chromosomal aberration associated with denovo and secondary myeloid malignancies." Gene Chromosomes Cancer. (in press).

林泰秀東京大学, 医学部・附属病院, 講師 (30238133)