Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7
Summary Monosomy 7 (−7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain‐of‐function SAMD9/9L variants and loss‐of‐function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associa...
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| Veröffentlicht in: | British journal of haematology 2020-12, Vol.191 (5), p.835-843 |
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| creator | Yoshida, Masanori Tanase‐Nakao, Kanako Shima, Hirohito Shirai, Ryota Yoshida, Kaoru Osumi, Tomoo Deguchi, Takao Mori, Makiko Arakawa, Yuki Takagi, Masatoshi Miyamura, Takako Sakaguchi, Kimiyoshi Toyoda, Hidemi Ishida, Hisashi Sakata, Naoki Imamura, Toshihiko Kawahara, Yuta Morimoto, Akira Koike, Takashi Yagasaki, Hiroshi Ito, Shuichi Tomizawa, Daisuke Kiyokawa, Nobutaka Narumi, Satoshi Kato, Motohiro |
| description | Summary
Monosomy 7 (−7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain‐of‐function SAMD9/9L variants and loss‐of‐function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with −7. However, the prevalence of the genetic variants among paediatric haematologic disorders with −7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with −7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next‐generation sequencing was used to detect low‐abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth‐restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with −7, and 40% of them were found to have some pathogenic germline variants in the three genes. |
| doi_str_mv | 10.1111/bjh.17006 |
| format | Article |
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Monosomy 7 (−7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain‐of‐function SAMD9/9L variants and loss‐of‐function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with −7. However, the prevalence of the genetic variants among paediatric haematologic disorders with −7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with −7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next‐generation sequencing was used to detect low‐abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth‐restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with −7, and 40% of them were found to have some pathogenic germline variants in the three genes.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/bjh.17006</identifier><identifier>PMID: 32770553</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Acute myeloid leukemia ; Adolescent ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, Pair 7 - genetics ; Female ; GATA2 ; GATA2 Transcription Factor - genetics ; Genetic diversity ; Germ-Line Mutation ; Hematologic Neoplasms - epidemiology ; Hematologic Neoplasms - genetics ; Hematology ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Infant, Newborn ; Intracellular Signaling Peptides and Proteins - genetics ; Leukemia ; Male ; Monosomy ; monosomy 7 ; Mutation ; Myelodysplastic syndrome ; Myelodysplastic Syndromes - epidemiology ; Myelodysplastic Syndromes - genetics ; Pediatrics ; Prevalence ; SAMD9 ; SAMD9L ; Tumor Suppressor Proteins - genetics</subject><ispartof>British journal of haematology, 2020-12, Vol.191 (5), p.835-843</ispartof><rights>2020 British Society for Haematology and John Wiley & Sons Ltd</rights><rights>2020 British Society for Haematology and John Wiley & Sons Ltd.</rights><rights>Copyright © 2020 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3876-2a97f687050404d30f08a6d6bdd7c1913cfb97c515926bca479e4882c11e09443</citedby><cites>FETCH-LOGICAL-c3876-2a97f687050404d30f08a6d6bdd7c1913cfb97c515926bca479e4882c11e09443</cites><orcidid>0000-0002-0192-7233 ; 0000-0002-3391-8403 ; 0000-0002-3226-556X ; 0000-0002-9171-7335 ; 0000-0002-9168-5409 ; 0000-0001-5536-6788 ; 0000-0001-5145-1774 ; 0000-0002-3665-401X ; 0000-0002-7580-9184</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbjh.17006$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbjh.17006$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32770553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoshida, Masanori</creatorcontrib><creatorcontrib>Tanase‐Nakao, Kanako</creatorcontrib><creatorcontrib>Shima, Hirohito</creatorcontrib><creatorcontrib>Shirai, Ryota</creatorcontrib><creatorcontrib>Yoshida, Kaoru</creatorcontrib><creatorcontrib>Osumi, Tomoo</creatorcontrib><creatorcontrib>Deguchi, Takao</creatorcontrib><creatorcontrib>Mori, Makiko</creatorcontrib><creatorcontrib>Arakawa, Yuki</creatorcontrib><creatorcontrib>Takagi, Masatoshi</creatorcontrib><creatorcontrib>Miyamura, Takako</creatorcontrib><creatorcontrib>Sakaguchi, Kimiyoshi</creatorcontrib><creatorcontrib>Toyoda, Hidemi</creatorcontrib><creatorcontrib>Ishida, Hisashi</creatorcontrib><creatorcontrib>Sakata, Naoki</creatorcontrib><creatorcontrib>Imamura, Toshihiko</creatorcontrib><creatorcontrib>Kawahara, Yuta</creatorcontrib><creatorcontrib>Morimoto, Akira</creatorcontrib><creatorcontrib>Koike, Takashi</creatorcontrib><creatorcontrib>Yagasaki, Hiroshi</creatorcontrib><creatorcontrib>Ito, Shuichi</creatorcontrib><creatorcontrib>Tomizawa, Daisuke</creatorcontrib><creatorcontrib>Kiyokawa, Nobutaka</creatorcontrib><creatorcontrib>Narumi, Satoshi</creatorcontrib><creatorcontrib>Kato, Motohiro</creatorcontrib><title>Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
Monosomy 7 (−7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain‐of‐function SAMD9/9L variants and loss‐of‐function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with −7. However, the prevalence of the genetic variants among paediatric haematologic disorders with −7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with −7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next‐generation sequencing was used to detect low‐abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth‐restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with −7, and 40% of them were found to have some pathogenic germline variants in the three genes.</description><subject>Acute myeloid leukemia</subject><subject>Adolescent</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromosome Deletion</subject><subject>Chromosomes, Human, Pair 7 - genetics</subject><subject>Female</subject><subject>GATA2</subject><subject>GATA2 Transcription Factor - genetics</subject><subject>Genetic diversity</subject><subject>Germ-Line Mutation</subject><subject>Hematologic Neoplasms - epidemiology</subject><subject>Hematologic Neoplasms - genetics</subject><subject>Hematology</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Leukemia</subject><subject>Male</subject><subject>Monosomy</subject><subject>monosomy 7</subject><subject>Mutation</subject><subject>Myelodysplastic syndrome</subject><subject>Myelodysplastic Syndromes - epidemiology</subject><subject>Myelodysplastic Syndromes - genetics</subject><subject>Pediatrics</subject><subject>Prevalence</subject><subject>SAMD9</subject><subject>SAMD9L</subject><subject>Tumor Suppressor Proteins - genetics</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PwzAQQC0EglIY-APIEhND6Dl27GQs5VtFIFHmyLGd1lUSFzst6r8nkMLGLbc8vTs9hM4IXJFuRsVycUUEAN9DA0J5EsWEkX00AAAREWDpEToOYQlAKCTkEB3RWAhIEjpA9tWbjaxMowx2JZ4bX1e2Mfh-PBvHWDYav42fb7JRNsUb6a1s2oBtg1fSaCtbbxVeSFPL1lVubpWssLbBeW18wJ-2XeDaNS64eovFCTooZRXM6W4P0fvd7WzyEE1f7h8n42mkaCp4FMtMlDzt3gMGTFMoIZVc80JroUhGqCqLTKiEJFnMCyWZyAxL01gRYiBjjA7RRe9defexNqHNl27tm-5kHjPOeUpBiI667CnlXQjelPnK21r6bU4g_46ad1Hzn6gde74zrova6D_yt2IHjHrg01Zm-78pv3566JVfNvV-mw</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Yoshida, Masanori</creator><creator>Tanase‐Nakao, Kanako</creator><creator>Shima, Hirohito</creator><creator>Shirai, Ryota</creator><creator>Yoshida, Kaoru</creator><creator>Osumi, Tomoo</creator><creator>Deguchi, Takao</creator><creator>Mori, Makiko</creator><creator>Arakawa, Yuki</creator><creator>Takagi, Masatoshi</creator><creator>Miyamura, Takako</creator><creator>Sakaguchi, Kimiyoshi</creator><creator>Toyoda, Hidemi</creator><creator>Ishida, Hisashi</creator><creator>Sakata, Naoki</creator><creator>Imamura, Toshihiko</creator><creator>Kawahara, Yuta</creator><creator>Morimoto, Akira</creator><creator>Koike, Takashi</creator><creator>Yagasaki, Hiroshi</creator><creator>Ito, Shuichi</creator><creator>Tomizawa, Daisuke</creator><creator>Kiyokawa, Nobutaka</creator><creator>Narumi, Satoshi</creator><creator>Kato, Motohiro</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0002-0192-7233</orcidid><orcidid>https://orcid.org/0000-0002-3391-8403</orcidid><orcidid>https://orcid.org/0000-0002-3226-556X</orcidid><orcidid>https://orcid.org/0000-0002-9171-7335</orcidid><orcidid>https://orcid.org/0000-0002-9168-5409</orcidid><orcidid>https://orcid.org/0000-0001-5536-6788</orcidid><orcidid>https://orcid.org/0000-0001-5145-1774</orcidid><orcidid>https://orcid.org/0000-0002-3665-401X</orcidid><orcidid>https://orcid.org/0000-0002-7580-9184</orcidid></search><sort><creationdate>202012</creationdate><title>Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7</title><author>Yoshida, Masanori ; Tanase‐Nakao, Kanako ; Shima, Hirohito ; Shirai, Ryota ; Yoshida, Kaoru ; Osumi, Tomoo ; Deguchi, Takao ; Mori, Makiko ; Arakawa, Yuki ; Takagi, Masatoshi ; Miyamura, Takako ; Sakaguchi, Kimiyoshi ; Toyoda, Hidemi ; Ishida, Hisashi ; Sakata, Naoki ; Imamura, Toshihiko ; Kawahara, Yuta ; Morimoto, Akira ; Koike, Takashi ; Yagasaki, Hiroshi ; Ito, Shuichi ; Tomizawa, Daisuke ; Kiyokawa, Nobutaka ; Narumi, Satoshi ; Kato, Motohiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3876-2a97f687050404d30f08a6d6bdd7c1913cfb97c515926bca479e4882c11e09443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute myeloid leukemia</topic><topic>Adolescent</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromosome Deletion</topic><topic>Chromosomes, Human, Pair 7 - genetics</topic><topic>Female</topic><topic>GATA2</topic><topic>GATA2 Transcription Factor - genetics</topic><topic>Genetic diversity</topic><topic>Germ-Line Mutation</topic><topic>Hematologic Neoplasms - epidemiology</topic><topic>Hematologic Neoplasms - genetics</topic><topic>Hematology</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Leukemia</topic><topic>Male</topic><topic>Monosomy</topic><topic>monosomy 7</topic><topic>Mutation</topic><topic>Myelodysplastic syndrome</topic><topic>Myelodysplastic Syndromes - epidemiology</topic><topic>Myelodysplastic Syndromes - genetics</topic><topic>Pediatrics</topic><topic>Prevalence</topic><topic>SAMD9</topic><topic>SAMD9L</topic><topic>Tumor Suppressor Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoshida, Masanori</creatorcontrib><creatorcontrib>Tanase‐Nakao, Kanako</creatorcontrib><creatorcontrib>Shima, Hirohito</creatorcontrib><creatorcontrib>Shirai, Ryota</creatorcontrib><creatorcontrib>Yoshida, Kaoru</creatorcontrib><creatorcontrib>Osumi, Tomoo</creatorcontrib><creatorcontrib>Deguchi, Takao</creatorcontrib><creatorcontrib>Mori, Makiko</creatorcontrib><creatorcontrib>Arakawa, Yuki</creatorcontrib><creatorcontrib>Takagi, Masatoshi</creatorcontrib><creatorcontrib>Miyamura, Takako</creatorcontrib><creatorcontrib>Sakaguchi, Kimiyoshi</creatorcontrib><creatorcontrib>Toyoda, Hidemi</creatorcontrib><creatorcontrib>Ishida, Hisashi</creatorcontrib><creatorcontrib>Sakata, Naoki</creatorcontrib><creatorcontrib>Imamura, Toshihiko</creatorcontrib><creatorcontrib>Kawahara, Yuta</creatorcontrib><creatorcontrib>Morimoto, Akira</creatorcontrib><creatorcontrib>Koike, Takashi</creatorcontrib><creatorcontrib>Yagasaki, Hiroshi</creatorcontrib><creatorcontrib>Ito, Shuichi</creatorcontrib><creatorcontrib>Tomizawa, Daisuke</creatorcontrib><creatorcontrib>Kiyokawa, Nobutaka</creatorcontrib><creatorcontrib>Narumi, Satoshi</creatorcontrib><creatorcontrib>Kato, Motohiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoshida, Masanori</au><au>Tanase‐Nakao, Kanako</au><au>Shima, Hirohito</au><au>Shirai, Ryota</au><au>Yoshida, Kaoru</au><au>Osumi, Tomoo</au><au>Deguchi, Takao</au><au>Mori, Makiko</au><au>Arakawa, Yuki</au><au>Takagi, Masatoshi</au><au>Miyamura, Takako</au><au>Sakaguchi, Kimiyoshi</au><au>Toyoda, Hidemi</au><au>Ishida, Hisashi</au><au>Sakata, Naoki</au><au>Imamura, Toshihiko</au><au>Kawahara, Yuta</au><au>Morimoto, Akira</au><au>Koike, Takashi</au><au>Yagasaki, Hiroshi</au><au>Ito, Shuichi</au><au>Tomizawa, Daisuke</au><au>Kiyokawa, Nobutaka</au><au>Narumi, Satoshi</au><au>Kato, Motohiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2020-12</date><risdate>2020</risdate><volume>191</volume><issue>5</issue><spage>835</spage><epage>843</epage><pages>835-843</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>Summary
Monosomy 7 (−7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain‐of‐function SAMD9/9L variants and loss‐of‐function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with −7. However, the prevalence of the genetic variants among paediatric haematologic disorders with −7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with −7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next‐generation sequencing was used to detect low‐abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth‐restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with −7, and 40% of them were found to have some pathogenic germline variants in the three genes.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>32770553</pmid><doi>10.1111/bjh.17006</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0192-7233</orcidid><orcidid>https://orcid.org/0000-0002-3391-8403</orcidid><orcidid>https://orcid.org/0000-0002-3226-556X</orcidid><orcidid>https://orcid.org/0000-0002-9171-7335</orcidid><orcidid>https://orcid.org/0000-0002-9168-5409</orcidid><orcidid>https://orcid.org/0000-0001-5536-6788</orcidid><orcidid>https://orcid.org/0000-0001-5145-1774</orcidid><orcidid>https://orcid.org/0000-0002-3665-401X</orcidid><orcidid>https://orcid.org/0000-0002-7580-9184</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acute myeloid leukemia Adolescent Child Child, Preschool Chromosome Deletion Chromosomes, Human, Pair 7 - genetics Female GATA2 GATA2 Transcription Factor - genetics Genetic diversity Germ-Line Mutation Hematologic Neoplasms - epidemiology Hematologic Neoplasms - genetics Hematology High-Throughput Nucleotide Sequencing Humans Infant Infant, Newborn Intracellular Signaling Peptides and Proteins - genetics Leukemia Male Monosomy monosomy 7 Mutation Myelodysplastic syndrome Myelodysplastic Syndromes - epidemiology Myelodysplastic Syndromes - genetics Pediatrics Prevalence SAMD9 SAMD9L Tumor Suppressor Proteins - genetics |
| title | Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7 |
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