1999 年度実績報告書

転座関連遺伝子変異を指標とした間期核FISH法による悪性リンパ腫の病型診断

研究課題

研究課題/領域番号	10670962
研究機関	京都府立医科大学
研究代表者	谷脇雅史京都府立医科大学, 医学部, 講師 (80163640)
研究分担者	奥田司京都府立医科大学, 医学部, 講師 (30291587)
キーワード	lymphoma / oncogene / IgH gene / FISH / diagnosis / MALT1 gene
研究概要	免疫グロブリンH(IgH)鎖遺伝子とリンパ腫関連遺伝子をプローブにして、間期核double-colorFISH(DC-FISH)法によって非ホジキンリンパ腫173例を検索し、70例(40.5%)にIgH転座を検出した。うち52例(74.3%)で相手遺伝子が同定でき、BCL2が19例、BCL6が16例、BCL1が11例、c-MYCが7例、PAX-5が2例であった。これらの相手遺伝子とWorkingFormulationの組織型との対応は乏しかったが、REAL分類では明確な対応の認められる病型があった。マントル細胞リンパ腫と診断された5例はすべてBCL1/IgH転座が陽性であり、PAX-5/IgH転座陽性の2例はlymphoplasmacytoid lymphomaであった。従って、IgH遺伝子の転座相手をFISHで検出することによって、REAL分類によるリンパ腫の診断をより正確に行うことができると考えられる。一方、IgH遺伝子転座の相手染色体が不明であった14q+をspectral karyotyping法で解析し、t(10;14)を2例、t(2;14)と11q13を切断点としないt(11;14)を各1例、同定できた。次に、MALTリンパ腫に特異的なt(11;18)(q21;q21)の18q21からMALT1を単離した。MALT1はリンパ造血細胞に優位に発現、免疫グロブリンのスーパーファミリーに属する構造を持ち、接着分子として機能している可能性がある。MALT1領域と11q21をカバーする人工酵母染色体をプローブにするDC-FISHによって、t(11;18)を間期核で検出する方法を確立した。B-NHL39例のうち4例(肺MALTリンパ腫3例と胃MALTリンパ腫1例)と、12例のマクログロブリン血症のうち1例でt(11;18)を検出した。

研究成果
(23件)

すべてその他

すべて文献書誌 (23件)

[文献書誌] Miwa H: "Induction of chromosomal aberrations and growth-transformation of lymphoblastoid cell lines by inhibition of reactive oxygen species-induced apoptosis with interleukin-6"Lab Invest. (in press).
[文献書誌] Hosokawa Y: "The Ikaros gene,a central regulator of lymphoid differentiation,fuses to the BCL6 gene as a result of t(3;7)(q27;p12)translocation in a patient with diffuse large B-cell lymophoma"Blood. (in press).
[文献書誌] Nakazawa N: "Interphase detection of t(4;14)(p16.3;q32.3)by in situ hybridization and FGFR3 overexpression in plasma cell malignancies"Cancer Genet Cytogenet. (in press).
[文献書誌] Shimizu S: "Identification of breakpoint cluster regions at 3q21 and 1p36.3 in hematological malignancies with t(1;3)(p36;q21)"Genes Chromosomes Cancer. 27・3. 229-238 (2000)
[文献書誌] Taki T: "AF5q31,a new member of the AF4-related genes,is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23)"Proc Natl Acad Sci USA. 96・25. 14535-14540 (1999)
[文献書誌] Sakakura C: "Bowel perforation during chemotherapy for non-hodgkin's lymphoma"Hepatogastroenterol. 46・30. 3175-3177 (1999)
[文献書誌] Sasai Y: "Genotype of glutathione S-transferase and other genetic configurations in myelodysplasia"Leukemia Res. 23・11. 975-981 (1999)
[文献書誌] Hamaguchi H: "A new translocation,t(2;4;12)(p21;q12;p13),in CD7-positive acute myeloid leukemia:A variant form of t(4;12)"Cancer Genet Cytogenet. 114・2. 96-99 (1999)
[文献書誌] Yoshida S: "Detection of MUM1/IRF4-IgH fusion in multiple myeloma"Leukemia. 13・11. 1812-1816 (1999)
[文献書誌] Kakazu N: "Combined spectral karyotyping and DAP1-banding analysis of chromosome abnormalities in myelodysplastic syndrome"Genes Chromosomes Cancer. 26・4. 336-345 (1999)
[文献書誌] Sonoki T: "A plasma cell leukemia patient showing bialleic 14q translocations:t(2;14)and t(11;14)"Acta Haematol(Basel). 101・4. 197-201 (1999)
[文献書誌] Akagi T: "A novel gene,MALT1 at 18q21,is involved in t(11;18)(q21;q21)found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue"Oncogene. 18・42. 5785-5794 (1999)
[文献書誌] Suzukawa K: "Activation of EVl1 transcripts with chromosomal translocation joining the TCRVβ locus and the EVl1 gene in human acute undifferentiated leukemia cell line(Kasumi-3)with a complex translocation of der(3)t(3;7;8)"Leukemia. 13・9. 1359-1366 (1999)
[文献書誌] Hirawake H: "Characterization of the human SDHD encoding the small subunit of cytochrome b(cybS)in mitochondrial succinate-ubiquinone oxidoreductase"Biochim Biophys Acta. 1412・3. 295-300 (1999)
[文献書誌] Nakamura T: "DANCE,a novel secreted RGD protein expressed in developing,atherosclerotic,and balloon injured arteries"J Biol Chem. 274・32. 22476-22483 (1999)
[文献書誌] Horiike S: "Distinct genetic involvement of the TP53 gene in therapy-related leukemia and myelodysplasia with chromosomal losses of nos.5 and/or 7,and its possible relationship to replication error phenotype"Leukemia. 13・8. 1235-1242 (1999)
[文献書誌] Kobayashi M: "Identification of a photoreceptor cell-specific nuclear receptor"Proc Natl Acad Sci USA. 96・9. 4814-4819 (1999)
[文献書誌] Lopez ND: "Isoform specific expression of the SDR-1 protein,α and β in subregions of adult rodent brain"Biomedical Res. 20・1. 43-49 (1999)
[文献書誌] Narita M: "Consistent detection of CALM-AF10 chimeric transcripts in haematological malignancies with t(10;11)(p13;q14)and identification of novel transcripts"Brit J Haematol. 105・4. 928-937 (1999)
[文献書誌] Yashige H: "Micronuclei and nuclear abnormalities observed in erythroblasts in myelodysplastic syndromes and in de novo acute leukemia after treatment"Acta Haematol(Basel). 101・1. 32-40 (1999)
[文献書誌] Akagi T: "Cytogenetic analysis of the breakpoint at 18q21.1 in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue"Genes Chromosomes Cancer. 24・4. 315-321 (1999)
[文献書誌] Iwai T: "Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia"Leukemia. 13・1. 38-43 (1999)
[文献書誌] Tani S: "Chromosomal mapping of two PBP-J-related genes:Kyo-T and PBP-L"J Hum Genet. 44・1. 73-75 (1999)

1999 年度 実績報告書

転座関連遺伝子変異を指標とした間期核FISH法による悪性リンパ腫の病型診断

研究代表者

谷脇 雅史 京都府立医科大学, 医学部, 講師 (80163640)

研究成果

[文献書誌] Miwa H: "Induction of chromosomal aberrations and growth-transformation of lymphoblastoid cell lines by inhibition of reactive oxygen species-induced apoptosis with interleukin-6"Lab Invest. (in press).

[文献書誌] Hosokawa Y: "The Ikaros gene,a central regulator of lymphoid differentiation,fuses to the BCL6 gene as a result of t(3;7)(q27;p12)translocation in a patient with diffuse large B-cell lymophoma"Blood. (in press).

[文献書誌] Nakazawa N: "Interphase detection of t(4;14)(p16.3;q32.3)by in situ hybridization and FGFR3 overexpression in plasma cell malignancies"Cancer Genet Cytogenet. (in press).

[文献書誌] Shimizu S: "Identification of breakpoint cluster regions at 3q21 and 1p36.3 in hematological malignancies with t(1;3)(p36;q21)"Genes Chromosomes Cancer. 27・3. 229-238 (2000)

[文献書誌] Taki T: "AF5q31,a new member of the AF4-related genes,is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23)"Proc Natl Acad Sci USA. 96・25. 14535-14540 (1999)

[文献書誌] Sakakura C: "Bowel perforation during chemotherapy for non-hodgkin's lymphoma"Hepatogastroenterol. 46・30. 3175-3177 (1999)

[文献書誌] Sasai Y: "Genotype of glutathione S-transferase and other genetic configurations in myelodysplasia"Leukemia Res. 23・11. 975-981 (1999)

[文献書誌] Hamaguchi H: "A new translocation,t(2;4;12)(p21;q12;p13),in CD7-positive acute myeloid leukemia:A variant form of t(4;12)"Cancer Genet Cytogenet. 114・2. 96-99 (1999)

[文献書誌] Yoshida S: "Detection of MUM1/IRF4-IgH fusion in multiple myeloma"Leukemia. 13・11. 1812-1816 (1999)

[文献書誌] Kakazu N: "Combined spectral karyotyping and DAP1-banding analysis of chromosome abnormalities in myelodysplastic syndrome"Genes Chromosomes Cancer. 26・4. 336-345 (1999)

[文献書誌] Sonoki T: "A plasma cell leukemia patient showing bialleic 14q translocations:t(2;14)and t(11;14)"Acta Haematol(Basel). 101・4. 197-201 (1999)

[文献書誌] Akagi T: "A novel gene,MALT1 at 18q21,is involved in t(11;18)(q21;q21)found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue"Oncogene. 18・42. 5785-5794 (1999)

[文献書誌] Suzukawa K: "Activation of EVl1 transcripts with chromosomal translocation joining the TCRVβ locus and the EVl1 gene in human acute undifferentiated leukemia cell line(Kasumi-3)with a complex translocation of der(3)t(3;7;8)"Leukemia. 13・9. 1359-1366 (1999)

[文献書誌] Hirawake H: "Characterization of the human SDHD encoding the small subunit of cytochrome b(cybS)in mitochondrial succinate-ubiquinone oxidoreductase"Biochim Biophys Acta. 1412・3. 295-300 (1999)

[文献書誌] Nakamura T: "DANCE,a novel secreted RGD protein expressed in developing,atherosclerotic,and balloon injured arteries"J Biol Chem. 274・32. 22476-22483 (1999)

[文献書誌] Horiike S: "Distinct genetic involvement of the TP53 gene in therapy-related leukemia and myelodysplasia with chromosomal losses of nos.5 and/or 7,and its possible relationship to replication error phenotype"Leukemia. 13・8. 1235-1242 (1999)

[文献書誌] Kobayashi M: "Identification of a photoreceptor cell-specific nuclear receptor"Proc Natl Acad Sci USA. 96・9. 4814-4819 (1999)

[文献書誌] Lopez ND: "Isoform specific expression of the SDR-1 protein,α and β in subregions of adult rodent brain"Biomedical Res. 20・1. 43-49 (1999)

[文献書誌] Narita M: "Consistent detection of CALM-AF10 chimeric transcripts in haematological malignancies with t(10;11)(p13;q14)and identification of novel transcripts"Brit J Haematol. 105・4. 928-937 (1999)

[文献書誌] Yashige H: "Micronuclei and nuclear abnormalities observed in erythroblasts in myelodysplastic syndromes and in de novo acute leukemia after treatment"Acta Haematol(Basel). 101・1. 32-40 (1999)

[文献書誌] Akagi T: "Cytogenetic analysis of the breakpoint at 18q21.1 in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue"Genes Chromosomes Cancer. 24・4. 315-321 (1999)

[文献書誌] Iwai T: "Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia"Leukemia. 13・1. 38-43 (1999)

[文献書誌] Tani S: "Chromosomal mapping of two PBP-J-related genes:Kyo-T and PBP-L"J Hum Genet. 44・1. 73-75 (1999)

1999 年度実績報告書

谷脇雅史京都府立医科大学, 医学部, 講師 (80163640)