The landscape of somatic mutations in Down syndrome–related myeloid disorders
Seishi Ogawa and colleagues report the landscape of somatic mutations in Down syndrome–related myeloid disorders. They identify recurrent mutations in multiple cohesin components, CTCF and epigenetic regulators in Down syndrome–related acute megakaryoblastic leukemia. Transient abnormal myelopoiesis...
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| Veröffentlicht in: | Nature genetics 2013-11, Vol.45 (11), p.1293-1299 |
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| creator | Yoshida, Kenichi Toki, Tsutomu Okuno, Yusuke Kanezaki, Rika Shiraishi, Yuichi Sato-Otsubo, Aiko Sanada, Masashi Park, Myoung-ja Terui, Kiminori Suzuki, Hiromichi Kon, Ayana Nagata, Yasunobu Sato, Yusuke Wang, RuNan Shiba, Norio Chiba, Kenichi Tanaka, Hiroko Hama, Asahito Muramatsu, Hideki Hasegawa, Daisuke Nakamura, Kazuhiro Kanegane, Hirokazu Tsukamoto, Keiko Adachi, Souichi Kawakami, Kiyoshi Kato, Koji Nishimura, Ryosei Izraeli, Shai Hayashi, Yasuhide Miyano, Satoru Kojima, Seiji Ito, Etsuro Ogawa, Seishi |
| description | Seishi Ogawa and colleagues report the landscape of somatic mutations in Down syndrome–related myeloid disorders. They identify recurrent mutations in multiple cohesin components,
CTCF
and epigenetic regulators in Down syndrome–related acute megakaryoblastic leukemia.
Transient abnormal myelopoiesis (TAM) is a myeloid proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous remission (DS-AMKL). Pathogenesis of these Down syndrome–related myeloid disorders is poorly understood, except for
GATA1
mutations found in most cases. Here we report genomic profiling of 41 TAM, 49 DS-AMKL and 19 non-DS-AMKL samples, including whole-genome and/or whole-exome sequencing of 15 TAM and 14 DS-AMKL samples. TAM appears to be caused by a single
GATA1
mutation and constitutive trisomy 21. Subsequent AMKL evolves from a pre-existing TAM clone through the acquisition of additional mutations, with major mutational targets including multiple cohesin components (53%),
CTCF
(20%), and
EZH2
,
KANSL1
and other epigenetic regulators (45%), as well as common signaling pathways, such as the JAK family kinases,
MPL
,
SH2B3
(
LNK
) and multiple RAS pathway genes (47%). |
| doi_str_mv | 10.1038/ng.2759 |
| format | Article |
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CTCF
and epigenetic regulators in Down syndrome–related acute megakaryoblastic leukemia.
Transient abnormal myelopoiesis (TAM) is a myeloid proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous remission (DS-AMKL). Pathogenesis of these Down syndrome–related myeloid disorders is poorly understood, except for
GATA1
mutations found in most cases. Here we report genomic profiling of 41 TAM, 49 DS-AMKL and 19 non-DS-AMKL samples, including whole-genome and/or whole-exome sequencing of 15 TAM and 14 DS-AMKL samples. TAM appears to be caused by a single
GATA1
mutation and constitutive trisomy 21. Subsequent AMKL evolves from a pre-existing TAM clone through the acquisition of additional mutations, with major mutational targets including multiple cohesin components (53%),
CTCF
(20%), and
EZH2
,
KANSL1
and other epigenetic regulators (45%), as well as common signaling pathways, such as the JAK family kinases,
MPL
,
SH2B3
(
LNK
) and multiple RAS pathway genes (47%).</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.2759</identifier><identifier>PMID: 24056718</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/514/1948 ; Agriculture ; Animal Genetics and Genomics ; Base Sequence ; Biomedicine ; Cancer ; Cancer Research ; CCCTC-Binding Factor ; Cell Cycle Proteins - genetics ; Cell Proliferation ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomes, Human, Pair 21 - genetics ; Cohesins ; Development and progression ; Down syndrome ; Down Syndrome - genetics ; Down Syndrome - immunology ; Enhancer of Zeste Homolog 2 Protein ; Epigenetics ; GATA1 Transcription Factor - genetics ; Gene Expression Profiling ; Gene Function ; Gene mutations ; Genes ; Genetic aspects ; Genomes ; Human Genetics ; Humans ; Identification and classification ; Leukemia ; Leukemia, Megakaryoblastic, Acute - genetics ; Leukemoid Reaction - genetics ; Mutation ; Myelodysplastic syndromes ; Myeloid Cells ; Myeloproliferative Disorders - genetics ; Nuclear Proteins - genetics ; Polycomb Repressive Complex 2 - genetics ; Repressor Proteins - genetics ; Science ; Sequence Analysis, DNA ; Technological change</subject><ispartof>Nature genetics, 2013-11, Vol.45 (11), p.1293-1299</ispartof><rights>Springer Nature America, Inc. 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Nov 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c576t-2ba791c0d12e22ffe9fcdb44b6c6a7a38e093ce791978d25752af96d78aaa12d3</citedby><cites>FETCH-LOGICAL-c576t-2ba791c0d12e22ffe9fcdb44b6c6a7a38e093ce791978d25752af96d78aaa12d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.2759$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.2759$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24056718$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoshida, Kenichi</creatorcontrib><creatorcontrib>Toki, Tsutomu</creatorcontrib><creatorcontrib>Okuno, Yusuke</creatorcontrib><creatorcontrib>Kanezaki, Rika</creatorcontrib><creatorcontrib>Shiraishi, Yuichi</creatorcontrib><creatorcontrib>Sato-Otsubo, Aiko</creatorcontrib><creatorcontrib>Sanada, Masashi</creatorcontrib><creatorcontrib>Park, Myoung-ja</creatorcontrib><creatorcontrib>Terui, Kiminori</creatorcontrib><creatorcontrib>Suzuki, Hiromichi</creatorcontrib><creatorcontrib>Kon, Ayana</creatorcontrib><creatorcontrib>Nagata, Yasunobu</creatorcontrib><creatorcontrib>Sato, Yusuke</creatorcontrib><creatorcontrib>Wang, RuNan</creatorcontrib><creatorcontrib>Shiba, Norio</creatorcontrib><creatorcontrib>Chiba, Kenichi</creatorcontrib><creatorcontrib>Tanaka, Hiroko</creatorcontrib><creatorcontrib>Hama, Asahito</creatorcontrib><creatorcontrib>Muramatsu, Hideki</creatorcontrib><creatorcontrib>Hasegawa, Daisuke</creatorcontrib><creatorcontrib>Nakamura, Kazuhiro</creatorcontrib><creatorcontrib>Kanegane, Hirokazu</creatorcontrib><creatorcontrib>Tsukamoto, Keiko</creatorcontrib><creatorcontrib>Adachi, Souichi</creatorcontrib><creatorcontrib>Kawakami, Kiyoshi</creatorcontrib><creatorcontrib>Kato, Koji</creatorcontrib><creatorcontrib>Nishimura, Ryosei</creatorcontrib><creatorcontrib>Izraeli, Shai</creatorcontrib><creatorcontrib>Hayashi, Yasuhide</creatorcontrib><creatorcontrib>Miyano, Satoru</creatorcontrib><creatorcontrib>Kojima, Seiji</creatorcontrib><creatorcontrib>Ito, Etsuro</creatorcontrib><creatorcontrib>Ogawa, Seishi</creatorcontrib><title>The landscape of somatic mutations in Down syndrome–related myeloid disorders</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Seishi Ogawa and colleagues report the landscape of somatic mutations in Down syndrome–related myeloid disorders. They identify recurrent mutations in multiple cohesin components,
CTCF
and epigenetic regulators in Down syndrome–related acute megakaryoblastic leukemia.
Transient abnormal myelopoiesis (TAM) is a myeloid proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous remission (DS-AMKL). Pathogenesis of these Down syndrome–related myeloid disorders is poorly understood, except for
GATA1
mutations found in most cases. Here we report genomic profiling of 41 TAM, 49 DS-AMKL and 19 non-DS-AMKL samples, including whole-genome and/or whole-exome sequencing of 15 TAM and 14 DS-AMKL samples. TAM appears to be caused by a single
GATA1
mutation and constitutive trisomy 21. Subsequent AMKL evolves from a pre-existing TAM clone through the acquisition of additional mutations, with major mutational targets including multiple cohesin components (53%),
CTCF
(20%), and
EZH2
,
KANSL1
and other epigenetic regulators (45%), as well as common signaling pathways, such as the JAK family kinases,
MPL
,
SH2B3
(
LNK
) and multiple RAS pathway genes (47%).</description><subject>631/208/514/1948</subject><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Base Sequence</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>CCCTC-Binding Factor</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Proliferation</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomes, Human, Pair 21 - genetics</subject><subject>Cohesins</subject><subject>Development and progression</subject><subject>Down syndrome</subject><subject>Down Syndrome - genetics</subject><subject>Down Syndrome - immunology</subject><subject>Enhancer of Zeste Homolog 2 Protein</subject><subject>Epigenetics</subject><subject>GATA1 Transcription Factor - genetics</subject><subject>Gene Expression Profiling</subject><subject>Gene Function</subject><subject>Gene mutations</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Leukemia</subject><subject>Leukemia, Megakaryoblastic, Acute - genetics</subject><subject>Leukemoid Reaction - genetics</subject><subject>Mutation</subject><subject>Myelodysplastic syndromes</subject><subject>Myeloid Cells</subject><subject>Myeloproliferative Disorders - genetics</subject><subject>Nuclear Proteins - genetics</subject><subject>Polycomb Repressive Complex 2 - genetics</subject><subject>Repressor Proteins - genetics</subject><subject>Science</subject><subject>Sequence Analysis, DNA</subject><subject>Technological 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Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoshida, Kenichi</au><au>Toki, Tsutomu</au><au>Okuno, Yusuke</au><au>Kanezaki, Rika</au><au>Shiraishi, Yuichi</au><au>Sato-Otsubo, Aiko</au><au>Sanada, Masashi</au><au>Park, Myoung-ja</au><au>Terui, Kiminori</au><au>Suzuki, Hiromichi</au><au>Kon, Ayana</au><au>Nagata, Yasunobu</au><au>Sato, Yusuke</au><au>Wang, RuNan</au><au>Shiba, Norio</au><au>Chiba, Kenichi</au><au>Tanaka, Hiroko</au><au>Hama, Asahito</au><au>Muramatsu, Hideki</au><au>Hasegawa, Daisuke</au><au>Nakamura, Kazuhiro</au><au>Kanegane, Hirokazu</au><au>Tsukamoto, Keiko</au><au>Adachi, Souichi</au><au>Kawakami, Kiyoshi</au><au>Kato, Koji</au><au>Nishimura, Ryosei</au><au>Izraeli, Shai</au><au>Hayashi, Yasuhide</au><au>Miyano, Satoru</au><au>Kojima, Seiji</au><au>Ito, Etsuro</au><au>Ogawa, Seishi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The landscape of somatic mutations in Down syndrome–related myeloid disorders</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>45</volume><issue>11</issue><spage>1293</spage><epage>1299</epage><pages>1293-1299</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><abstract>Seishi Ogawa and colleagues report the landscape of somatic mutations in Down syndrome–related myeloid disorders. They identify recurrent mutations in multiple cohesin components,
CTCF
and epigenetic regulators in Down syndrome–related acute megakaryoblastic leukemia.
Transient abnormal myelopoiesis (TAM) is a myeloid proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous remission (DS-AMKL). Pathogenesis of these Down syndrome–related myeloid disorders is poorly understood, except for
GATA1
mutations found in most cases. Here we report genomic profiling of 41 TAM, 49 DS-AMKL and 19 non-DS-AMKL samples, including whole-genome and/or whole-exome sequencing of 15 TAM and 14 DS-AMKL samples. TAM appears to be caused by a single
GATA1
mutation and constitutive trisomy 21. Subsequent AMKL evolves from a pre-existing TAM clone through the acquisition of additional mutations, with major mutational targets including multiple cohesin components (53%),
CTCF
(20%), and
EZH2
,
KANSL1
and other epigenetic regulators (45%), as well as common signaling pathways, such as the JAK family kinases,
MPL
,
SH2B3
(
LNK
) and multiple RAS pathway genes (47%).</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>24056718</pmid><doi>10.1038/ng.2759</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2013-11, Vol.45 (11), p.1293-1299 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1554943165 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 631/208/514/1948 Agriculture Animal Genetics and Genomics Base Sequence Biomedicine Cancer Cancer Research CCCTC-Binding Factor Cell Cycle Proteins - genetics Cell Proliferation Chromosomal Proteins, Non-Histone - genetics Chromosomes, Human, Pair 21 - genetics Cohesins Development and progression Down syndrome Down Syndrome - genetics Down Syndrome - immunology Enhancer of Zeste Homolog 2 Protein Epigenetics GATA1 Transcription Factor - genetics Gene Expression Profiling Gene Function Gene mutations Genes Genetic aspects Genomes Human Genetics Humans Identification and classification Leukemia Leukemia, Megakaryoblastic, Acute - genetics Leukemoid Reaction - genetics Mutation Myelodysplastic syndromes Myeloid Cells Myeloproliferative Disorders - genetics Nuclear Proteins - genetics Polycomb Repressive Complex 2 - genetics Repressor Proteins - genetics Science Sequence Analysis, DNA Technological change |
| title | The landscape of somatic mutations in Down syndrome–related myeloid disorders |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T19%3A07%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20landscape%20of%20somatic%20mutations%20in%20Down%20syndrome%E2%80%93related%20myeloid%20disorders&rft.jtitle=Nature%20genetics&rft.au=Yoshida,%20Kenichi&rft.date=2013-11-01&rft.volume=45&rft.issue=11&rft.spage=1293&rft.epage=1299&rft.pages=1293-1299&rft.issn=1061-4036&rft.eissn=1546-1718&rft_id=info:doi/10.1038/ng.2759&rft_dat=%3Cgale_proqu%3EA350977030%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1467256349&rft_id=info:pmid/24056718&rft_galeid=A350977030&rfr_iscdi=true |