1999 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	10670962
Research Institution	KYOTO PREFECTURAL UNIVERSITY OF MEDICINE
Principal Investigator	谷脇雅史京都府立医科大学, 医学部, 講師 (80163640)
Co-Investigator(Kenkyū-buntansha)	奥田司京都府立医科大学, 医学部, 講師 (30291587)
Keywords	lymphoma / oncogene / IgH gene / FISH / diagnosis / MALT1 gene
Research Abstract	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。

Research Products
(23 results)

All Other

All Publications (23 results)

[Publications] 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).
[Publications] 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).
[Publications] 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).
[Publications] 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)
[Publications] 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)
[Publications] Sakakura C: "Bowel perforation during chemotherapy for non-hodgkin's lymphoma"Hepatogastroenterol. 46・30. 3175-3177 (1999)
[Publications] Sasai Y: "Genotype of glutathione S-transferase and other genetic configurations in myelodysplasia"Leukemia Res. 23・11. 975-981 (1999)
[Publications] 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)
[Publications] Yoshida S: "Detection of MUM1/IRF4-IgH fusion in multiple myeloma"Leukemia. 13・11. 1812-1816 (1999)
[Publications] Kakazu N: "Combined spectral karyotyping and DAP1-banding analysis of chromosome abnormalities in myelodysplastic syndrome"Genes Chromosomes Cancer. 26・4. 336-345 (1999)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Nakamura T: "DANCE,a novel secreted RGD protein expressed in developing,atherosclerotic,and balloon injured arteries"J Biol Chem. 274・32. 22476-22483 (1999)
[Publications] 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)
[Publications] Kobayashi M: "Identification of a photoreceptor cell-specific nuclear receptor"Proc Natl Acad Sci USA. 96・9. 4814-4819 (1999)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Iwai T: "Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia"Leukemia. 13・1. 38-43 (1999)
[Publications] Tani S: "Chromosomal mapping of two PBP-J-related genes:Kyo-T and PBP-L"J Hum Genet. 44・1. 73-75 (1999)

1999 Fiscal Year Annual Research Report

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

Principal Investigator

谷脇 雅史 京都府立医科大学, 医学部, 講師 (80163640)

Research Products

[Publications] 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).

[Publications] 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).

[Publications] 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).

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

谷脇雅史京都府立医科大学, 医学部, 講師 (80163640)