Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones
During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one w...
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description | During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/ radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis. |
doi_str_mv | 10.1038/sj.leu.2402188 |
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J ; DAVIS, E. M ; GILL SUPER, H ; ESPINOSA III, R ; LE BEAU, M. M ; ROWLEY, J. D</creator><creatorcontrib>SATO, Y ; KOBAYASHI, H ; SUTO, Y ; OLNEY, H. J ; DAVIS, E. M ; GILL SUPER, H ; ESPINOSA III, R ; LE BEAU, M. M ; ROWLEY, J. D</creatorcontrib><description>During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/ radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2402188</identifier><identifier>PMID: 11480561</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Biological and medical sciences ; Blood cancer ; Cancer ; Care and treatment ; chromosome 12 ; Chromosome banding ; Chromosome Fragility ; Chromosome rearrangements ; Chromosome translocations ; Chromosomes ; Chromosomes, Human, Pair 12 ; Cloning ; Cyclin-dependent kinase inhibitor p27 ; Cytogenetics ; Fluorescence ; Fluorescence in situ hybridization ; Gene Rearrangement ; Genetic aspects ; Genomic instability ; Hematologic and hematopoietic diseases ; Hematologic Neoplasms - genetics ; Hematology ; Humans ; In situ hybridization ; Karyotypes ; Kinases ; KIP1/CDKN1 gene ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical prognosis ; Medical sciences ; Metaphase ; Mutagens ; Oncology ; Patients ; Radiation therapy ; Segments ; TEL/ETV6 gene ; Transcription factors</subject><ispartof>Leukemia, 2001-08, Vol.15 (8), p.1193-1202</ispartof><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2001 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2001</rights><rights>Macmillan Publishers Limited 2001.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c545t-4f3a00afffbce7529b7bc98278401995711b3b40e4cef506ccd4ddfbbbeb1b413</citedby><cites>FETCH-LOGICAL-c545t-4f3a00afffbce7529b7bc98278401995711b3b40e4cef506ccd4ddfbbbeb1b413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14102161$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11480561$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SATO, Y</creatorcontrib><creatorcontrib>KOBAYASHI, H</creatorcontrib><creatorcontrib>SUTO, Y</creatorcontrib><creatorcontrib>OLNEY, H. J</creatorcontrib><creatorcontrib>DAVIS, E. M</creatorcontrib><creatorcontrib>GILL SUPER, H</creatorcontrib><creatorcontrib>ESPINOSA III, R</creatorcontrib><creatorcontrib>LE BEAU, M. M</creatorcontrib><creatorcontrib>ROWLEY, J. D</creatorcontrib><title>Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/ radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis.</description><subject>Biological and medical sciences</subject><subject>Blood cancer</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>chromosome 12</subject><subject>Chromosome banding</subject><subject>Chromosome Fragility</subject><subject>Chromosome rearrangements</subject><subject>Chromosome translocations</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 12</subject><subject>Cloning</subject><subject>Cyclin-dependent kinase inhibitor p27</subject><subject>Cytogenetics</subject><subject>Fluorescence</subject><subject>Fluorescence in situ hybridization</subject><subject>Gene Rearrangement</subject><subject>Genetic aspects</subject><subject>Genomic instability</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematologic Neoplasms - genetics</subject><subject>Hematology</subject><subject>Humans</subject><subject>In situ hybridization</subject><subject>Karyotypes</subject><subject>Kinases</subject><subject>KIP1/CDKN1 gene</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Metaphase</subject><subject>Mutagens</subject><subject>Oncology</subject><subject>Patients</subject><subject>Radiation therapy</subject><subject>Segments</subject><subject>TEL/ETV6 gene</subject><subject>Transcription factors</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kk2PFCEQhjtG466rV4-mo3FvPQIN_eFtM_Er2cSLngnQxQwjDSPQifND_L_W6JhRs4YDpN6n3gKqquopJStK2uFV3q08LCvGCaPDcK-6pLzvGiEEvV9dkmHom25k_KJ6lPOOkKPYPawuKOUDER29rL6vtynOMcdZ-dqFXJR23pUDnmvzW4JaqzDVlO1p-7qeF1_c3mMwgfqSaw9qcmFTl1ibOKPwrUYhJRU2MEMoGb2MX34y5lDiBgIUZ5T3h3oJExQwWBX98qIb42OA_Lh6YJXP8OS0X1Wf3775tH7f3H5892F9c9sYwUVpuG0VIcpaqw30go2612YcWD9wQsdR9JTqVnMC3IAVpDNm4tNktdagqea0vaquf_nuU_y6QC5ydtmA9ypAXLKk_Ug47TiCL_4Bd3FJAe8mWcexEB_piNTz_1KMCMbEQM5WG-VBumBjScoc68obRsjIetK2SK3uoHBNMDuDf2Qdxv9KuP4jYQvKl22Ofikuhnyns0kx5wRW7pObVTpISuRxpmTeSZwpeZopTHh2etWiZ5jO-GmIEHh5AlTGtlrsvHH5zHGKRsj9AB9f1ds</recordid><startdate>20010801</startdate><enddate>20010801</enddate><creator>SATO, Y</creator><creator>KOBAYASHI, H</creator><creator>SUTO, Y</creator><creator>OLNEY, H. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Metaphase</topic><topic>Mutagens</topic><topic>Oncology</topic><topic>Patients</topic><topic>Radiation therapy</topic><topic>Segments</topic><topic>TEL/ETV6 gene</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SATO, Y</creatorcontrib><creatorcontrib>KOBAYASHI, H</creatorcontrib><creatorcontrib>SUTO, Y</creatorcontrib><creatorcontrib>OLNEY, H. J</creatorcontrib><creatorcontrib>DAVIS, E. M</creatorcontrib><creatorcontrib>GILL SUPER, H</creatorcontrib><creatorcontrib>ESPINOSA III, R</creatorcontrib><creatorcontrib>LE BEAU, M. M</creatorcontrib><creatorcontrib>ROWLEY, J. 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J</au><au>DAVIS, E. M</au><au>GILL SUPER, H</au><au>ESPINOSA III, R</au><au>LE BEAU, M. M</au><au>ROWLEY, J. D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones</atitle><jtitle>Leukemia</jtitle><addtitle>Leukemia</addtitle><date>2001-08-01</date><risdate>2001</risdate><volume>15</volume><issue>8</issue><spage>1193</spage><epage>1202</epage><pages>1193-1202</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/ radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>11480561</pmid><doi>10.1038/sj.leu.2402188</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biological and medical sciences Blood cancer Cancer Care and treatment chromosome 12 Chromosome banding Chromosome Fragility Chromosome rearrangements Chromosome translocations Chromosomes Chromosomes, Human, Pair 12 Cloning Cyclin-dependent kinase inhibitor p27 Cytogenetics Fluorescence Fluorescence in situ hybridization Gene Rearrangement Genetic aspects Genomic instability Hematologic and hematopoietic diseases Hematologic Neoplasms - genetics Hematology Humans In situ hybridization Karyotypes Kinases KIP1/CDKN1 gene Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical prognosis Medical sciences Metaphase Mutagens Oncology Patients Radiation therapy Segments TEL/ETV6 gene Transcription factors |
title | Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones |
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